Fungicides

ABSTRACT

This invention relates to novel derivatives of pyridopyrazines and pyridopyridazines, to processes for preparing them, to intermediate chemicals used in their manufacture, to compositions containing them and to methods of using them to combat fungi, especially fungal infections of plants. The fungicidal compounds have the general formula (1) wherein R, R 1 , R 2 , W, X Y and Z are defined in the specification

This application is a division of application Ser. No. 10/540,035 filed Jun. 22, 2006, still pending, which is the National Stage of International Application No. PCT/GB2003/005250, filed Dec. 3, 2003, which claims the benefit of Great Britain Application No. 0230020.0, filed Dec. 23, 2002, all of which are incorporated herein by reference.

This invention relates to novel derivatives of pyridopyrazines and pyridopyridazines, to processes for preparing them, to certain intermediate chemicals used in their manufacture, to compositions containing them and to methods of using them to combat fungi, especially fungal infections of plants.

Derivatives of the nitrogen-containing 5,6 ring system s-1,2,4-triazolo[1,5-a]pyrimidine are known from the patent literature as being useful for controlling phytopathogenic fungi. Examples of recent patent publications include EP-A-1249452, WO 02/051845, WO 02/083676, WO 02/083677, WO 02/088125, WO 02/088126, WO 02/088127. Condensed nitrogen heterocycles used as antimycotics are known from U.S. Pat. No. 5,821,244. Derivatives of pyridopyrazines are known in the chemical literature, for example from J. Med. Chem. (1968), 11(6), 1216-18, J. Med. Chem. (1970), 13(5), 853-7 and U.S. Pat. No. 3,984,412, but not for agrochemical purposes.

The present invention is concerned with the provision of novel pyridopyrazines and pyridopyridazines for combating phytopathogenic diseases on plants and harvested food crops.

Thus, according to the present invention, there is provided a compound of the general formula (1):

wherein W and X, W and Z, X and Y or Y and Z are N and the other two are CR⁸; R⁸ is H, halo, C₁₋₄ alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkyl; R is halo; R¹ is halo, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl, C₁₋₈ alkoxy, C₁₋₈ alkylthio, aryl, aryloxy, arylthio, heteroaryl, heteroaryloxy, heteroarylthio, aryl(C₁₋₄)alkyl, aryl(C₁₋₄)alkoxy, heteroaryl(C₁₋₄)alkyl, heteroaryl(C₁₋₄)alkoxy, aryl(C₁₋₄)alkylthio, heteroaryl(C₁₋₄)alkylthio, morpholino, piperidino or pyrrolidino;

R² is NR³R⁴;

R³ and R⁴ are independently H, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, aryl, aryl(C₁₋₈)alkyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl, heteroaryl, heteroaryl(C₁₋₈)alkyl, NR⁵R⁶, provided that not both R³ and R⁴ are H or NR⁵R⁶, or R³ and R⁴ together form a C₃₋₇ alkylene or C₃₋₇ alkenylene chain optionally substituted with one or more C₁₋₄ alkyl or C₁₋₄ alkoxy groups, or, together with the nitrogen atom to which they are attached, R³ and R⁴ form a morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or piperazine N—(C₁₋₄)alkyl (especially N-methyl) ring; and R⁵ and R⁶ are independently H, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, aryl, aryl(C₁₋₈)alkyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl, heteroaryl or heteroaryl(C₁₋₈)alkyl; any of the foregoing alkyl, alkenyl, alkynyl or cycloalkyl groups or moieties (other than for R⁸) being optionally substituted with halogen, cyano, C₁₋₆ alkoxy, C₁₋₆ alkylcarbonyl, C₁₋₆ alkoxycarbonyl, C₁₋₆ haloalkoxy, C₁₋₆ alkylthio, tri(C₁₋₄)alkylsilyl, C₁₋₆ alkylamino or C₁₋₆ dialkylamino, any of the foregoing morpholine, thiomorpholine, piperidine, piperazine and pyrrolidine rings being optionally substituted with C₁₋₄ alkyl (especially methyl), and any of the foregoing aryl or heteroaryl groups or moieties being optionally substituted with one or more substituents selected from halo, hydroxy, mercapto, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ alkoxy, C₂₋₆ alkenyloxy, C₂₋₆ alkynyloxy, halo(C₁₋₆)alkyl, halo(C₁₋₆)alkoxy, C₁₋₆ alkylthio, halo(C₁₋₆)alkylthio, hydroxy(C₁₋₆)alkyl, C₁₋₄ alkoxy(C₁₋₆)alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenoxy, benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato, isothiocyanato, nitro, —NR′″R″″, —NHCOR′″, —NHCONR′″R″″, —CONR′″R″″, —SO₂R′″, —OSO₂R′″, —COR′″, —CR′″═NR″″ or —N═CR′″R″″, in which R′″ and R″″ are independently hydrogen, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy, halo(C₁₋₄)alkoxy, C₁₋₄ alkylthio, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenyl or benzyl, the phenyl and benzyl groups being optionally substituted with halogen, C₁₋₄ alkyl or C₁₋₄ alkoxy.

The invention includes a compound of the general formula (1) as defined immediately above except that: C₁₋₈ alkoxy and C₁₋₈ alkylthio are excluded as values of R and R²; C₇ alkylene and C₃₋₇ alkenylene are excluded as chains formed by R³ and R⁴; the C₃₋₆ chain that R³ and R⁴ may form may only be optionally substituted with one or more methyl groups; thiomorpholine, thiomorpholine S-oxide, thiomorpholine S-dioxide and piperazine are excluded as rings that R³ and R⁴ may form; tri(C₁₋₄)alkylsilyl is excluded as a substituent of any alkyl, alkenyl, alkynyl or cycloalkyl group or moiety and any morpholine, piperidine or pyrrolidine ring is unsubstituted.

The compounds of the invention may contain one or more asymmetric carbon atoms and may exist as enantiomers (or as pairs of diastereoisomers) or as mixtures of such. They may also exist as diastereoisomers by virtue of restricted rotation about a bond. However, mixtures of enantiomers or diastereoisomers may be separated into individual isomers or isomer pairs, and this invention embraces such isomers and mixtures thereof in all proportions. It is to be expected that for any given compound, one isomer may be more fungicidally active than another.

Except where otherwise stated, alkyl groups and alkyl moieties of alkoxy, alkylthio, etc., contain from 1 to 8, suitably from 1 to 6 and typically from 1 to 4, carbon atoms in the form of straight or branched chains. Examples are methyl, ethyl, n- and iso-propyl, n-, sec-, iso- and tert-butyl, n-pentyl and n-hexyl. Cycloalkyl groups contain from 3 to 8, typically from 3 to 6, carbon atoms and include bicycloalkyl groups such as the bicyclo[2.2.1]heptyl group. Haloalkyl groups or moieties are typically trichloromethyl or trifluoromethyl or contain a trichloromethyl or trifluoromethyl terminal group.

Except where otherwise stated, alkenyl and alkynyl moieties also contain from 2 to 8, suitably from 2 to 6 and typically from 2 to 4, carbon atoms in the form of straight or branched chains. Examples are allyl, 2-methylallyl and propargyl. Optional substituents include halo, typically fluoro. An example of halo-substituted alkenyl is 3,4,4-trifluoro-n-butenyl.

Halo includes fluoro, chloro, bromo and iodo. Most commonly it is fluoro, chloro or bromo and usually fluoro or chloro.

Aryl is usually phenyl but also includes naphthyl, anthryl and phenanthryl.

Heteroaryl is typically a 5- or 6-membered aromatic ring containing one or more O, N or S heteroatoms, which may be fused to one or more other aromatic or heteroaromatic rings, such as a benzene ring. Examples are thienyl, furyl, pyrrolyl, isoxazolyl, oxazolyl, oxadiazolyl, pyrazolyl, imidazolyl, triazolyl, isothiazolyl, tetrazolyl, thiadiazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, benzofuryl, benzothienyl, dibenzofuryl, benzothiazolyl, benzoxazolyl, benzimidazolyl, indolyl, quinolinyl and quinoxalinyl groups and, where appropriate, N-oxides thereof.

The 6,6-ring systems embraced by the general formula (1) are pyrido[2,3-c]pyridazines (where W and X are both CR⁸ and Y and Z are both N), pyrido[2,3-d]pyridazines (where W and Z are both CR⁸ and X and Y are both N), pyrido[3,2-c]pyridazines (where Y and Z are both CR⁸ and W and X are both N) and pyrido[2,3-b]pyrazine (where X and Y are both CR⁸ and W and Z are both N). Of particular interest are pyrido[2,3-b]pyrazines.

R⁸, which may be the same or different for the two CR⁸ values of W, X, Y and Z, is H, halo (for example bromo), C₁₋₄ alkyl (for example methyl), C₁₋₄ alkoxy (for example methoxy) or halo(C₁₋₄)alkyl (for example trifluoromethyl). Usually R⁸ will be H.

R is halo, especially chloro or fluoro, and R² is NR³R⁴. In the case of pyrido[2,3-b]pyrazine ring systems, the more active compounds are those where R² is NR³R⁴. R³ is typically C₁₋₈ alkyl (for example ethyl, n-propyl, n-butyl, sec-butyl (the S- or R-isomer or the racemate) and tert-butyl), halo(C₁₋₈)alkyl (for example 2, 2,2-trifluoroethyl, 2,2,2-trifluoro-1-methylethyl (the S- or R-isomer or the racemate), 3,3,3-trifluoropropyl and 4,4,4-trifluorobutyl), hydroxy(C₁₋₈)alkyl (for example hydroxyethyl), C₁₋₄ alkoxy(C₁₋₈)alkyl (for example methoxymethyl and methoxy-iso-butyl), C₁₋₄ alkoxyhalo(C₁₋₈)alkyl (for example 2-methoxy-2-trifluoromethylethyl), tri(C₁₋₄)alkylsilyl(C₁₋₆)alkyl (for example trimethylsilylmethyl), C₁₋₄ alkylcarbonyl(C₁₋₈)alkyl (for example 1-acetylethyl and 1-tert-butylcarbonylethyl), C₁₋₄ alkylcarbonylhalo(C₁₋₈)alkyl (for example 1-acetyl-2,2,2-trifluoroethyl), phenyl(₁₋₄)alkyl (for example benzyl), C₂₋₈ alkenyl (for example allyl and methylallyl), halo(C₂₋₈)alkenyl (for example 3-methyl-4,4-difluorobut-3-enyl), C₂₋₈ alkynyl (for example propargyl), C₃₋₈ cycloalkyl (for example cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl) optionally substituted with chloro, fluoro or methyl, C₃₋₈ cycloalkyl(C₁₋₄)alkyl (for example cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl and cyclohexylmethyl), phenylamino, piperidino or morpholino, the phenyl ring of phenylalkyl or phenylamino being optionally substituted with one, two or three substituents selected from halo (typically fluoro, chloro or bromo), C₁₋₄ alkyl (typically methyl), halo(C₁₋₄)alkyl (typically trifluoromethyl), C₁₋₄ alkoxy (typically methoxy) and halo(C₁₋₄)alkoxy (typically trifluoromethoxy). R⁴ is typically H, C₁₋₄ alkyl (for example ethyl and n-propyl), halo(C₁₋₄)alkyl (for example 2,2,2-trifluoroethyl) or amino. Alternatively R³ and R⁴ together form a C₄₋₆ alkylene chain optionally substituted with methyl, for example 3-methylpentylene, or, together with the nitrogen atom to which they are attached, R³ and R⁴ form a morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or piperazine N—(C₁₋₄)alkyl (especially N-methyl) ring, in which the morpholine or piperazine rings are optionally substituted with methyl.

Typically R¹ is phenyl optionally substituted with from one to five halogen atoms, particularly fluorine and chlorine atoms and especially fluorine atoms or with from one to three substituents selected from halo (for example fluoro and chloro), C₁₋₄ alkyl (for example methyl), halo(C₁₋₄)alkyl (for example trifluoromethyl), C₁₋₄ alkoxy (for example methoxy) or halo(C₁₋₄)alkoxy (for example trifluoromethoxy). Examples are 2,6-difluorophenyl, 2-fluoro-6-chlorophenyl, 2,5,6-trifluorophenyl, 2,4,6-trifluorophenyl, 2,6-difluoro-4-methoxyphenyl, pentafluorophenyl, 2-fluorophenyl, 2,3,5,6-tetrafluorophenyl, 2-chloro-4,6-difluorophenyl, 2-chlorophenyl, 2,6-dichlorophenyl, 2,4-dichlorophenyl, 2,4,6-trichlorophenyl, 2,3,6-tri-chlorophenyl, pentachlorophenyl, 2-fluoro-4,6-dichlorophenyl, 4-fluoro-2,6-dichlorophenyl, 2-bromophenyl, 2-fluoro-6-bromophenyl, 2-bromo-4,6-difluorophenyl, 2-fluoro-6-methylphenyl, 2-chloro-6-methylphenyl, 2-methoxyphenyl, 2,6-dimethoxyphenyl, 2-fluoro-6-methoxyphenyl, 2-trifluoromethylphenyl, 2-fluoro-6-trifluoromethylphenyl, 2,6-di-(trifluoromethyl)phenyl, 2-chloro-6-trifluoromethylphenyl, 2,4-difluoro-6-trifluoromethylphenyl, 2,4-difluoro-6-methoxyphenyl and 2,4-difluoro-6-methylphenyl.

Also of particular interest are compounds where R¹ is pyridyl optionally substituted with from one to four halogen atoms or with from one to three substituents selected from halo (for example fluoro and chloro), C₁₋₄ alkyl (for example methyl), halo(C₁₋₄)alkyl (for example trifluoromethyl), C₁₋₄ alkoxy (for example methoxy) or halo(C₁₋₄)alkoxy (for example trifluoromethoxy). Examples are 2,4-difluoropyrid-3-yl, 3,5-difluoropyrid-4-yl, tetrafluoropyrid-4-yl, 3-fluoropyrid-2-yl, 4-fluoropyrid-3-yl, 3-fluoropyrid-4-yl, 2-fluoropyrid-3-yl, 2,4,6-trifluoropyrid-3-yl, 3,5-difluoropyrid-2-yl, 2,6-difluoropyrid-3-yl, 2,4-difluoro-6-methoxypyrid-3-yl, 2-fluoro-4-chloropyrid-3-yl, 3-fluoro-5-chloropyrid-4-yl, 2-chloro-4-fluoropyrid-3-yl, 2,4-dichloropyrid-3-yl, 3-chloropyrid-2-yl 1,4-chloropyrid-3-yl, 3-chloropyrid-4-yl, 2-chloropyrid-3-yl, 3-trifluoromethylpyrid-2-yl, 4-trifluoromethylpyrid-3-yl, 3,5-dichloropyrid-2-yl, 4,6-dichloropyrid-3-yl, 3-trifluoromethylpyrid-4-yl, 2-trifluoromethylpyrid-3-yl, 2-fluoro-4-trifluoromethylpyrid-3-yl, 3-fluoro-5-trifluoromethylpyrid-4-yl, 4-fluoro-2-trifluoromethylpyrid-3-yl, 2,6-dichloropyrid-3-yl, 3,5-dichloropyrid-4-yl, 3-chloro-6-trifluoromethylpyrid-2-yl, 3-fluoro-6-trifluoromethylpyrid-2-yl, pyrid-2-yl, pyrid-3-yl and pyrid-4-yl.

Also of particular interest are compounds where R¹ is 2- or 3-thienyl optionally substituted with from one to three halogen atoms or with from one to three substituents selected from halo (for example fluoro and chloro), C₁₋₄ alkyl (for example methyl), halo-(C₁₋₄)alkyl (for example trifluoromethyl), C₁₋₄ alkoxy (for example methoxy) or halo(C₁₋₄)alkoxy (for example trifluoromethoxy). Examples are 3-fluorothien-2-yl, 3-chlorothien-2-yl, 2,4-difluorothien-3-yl, 2,4-dichlorothien-3-yl and 2,4,5-trichlorothien-3-yl.

Examples of other values of R¹ of especial interest are unsubstituted piperidino and morpholino, 2-methylpiperidino, 2,6-dimethylpiperidino and 2,6-dimethylmorpholino.

In one aspect the invention provides a compound of the general formula (1) wherein W and X, W and Z, X and Y or Y and Z are N and the other two are CR⁸;

R⁸ is H, halo, C₁₋₄ alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkyl; R is halo; R¹ is halo, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl, C₁₋₈ alkoxy, C₁₋₈ alkylthio, aryl, aryloxy, arylthio, heteroaryl, heteroaryloxy, heteroarylthio, aryl(C₁₋₄)alkyl, aryl(C₁₋₄)alkoxy, heteroaryl(C₁₋₄)alkyl, heteroaryl(C₁₋₄)alkoxy, aryl(C₁₋₄)alkylthio, heteroaryl(C₁₋₄)alkylthio, morpholino, piperidino or pyrrolidino;

R² is NR³R⁴;

R³ and R⁴ are independently H, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, aryl, aryl(C₁₋₈)alkyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl, heteroaryl, heteroaryl(C₁₋₈)alkyl, NR⁵R⁶, provided that not both R³ and R⁴ are H or NR⁵R⁶, or R³ and R⁴ together form a C₃₋₇ alkylene or C₃₋₇ alkenylene chain optionally substituted with one or more C₁₋₄ alkyl or C₁₋₄ alkoxy groups, or, together with the nitrogen atom to which they are attached, R³ and R⁴ form a morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or piperazine N—(C₁₋₄)alkyl (especially N-methyl) ring; and R⁵ and R⁶ are independently H, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, aryl, aryl(C₁₋₈)alkyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl, heteroaryl or heteroaryl(C₁₋₈)alkyl; any of the foregoing alkyl, alkenyl, alkynyl or cycloalkyl groups or moieties (other than for R⁸) being optionally substituted with halogen, cyano, C₁₋₆ alkoxy, C₁₋₆ alkylcarbonyl, C₁₋₆ alkoxycarbonyl, C₁₋₆ haloalkoxy, C₁₋₆ alkylthio, tri(C₁₋₄)alkylsilyl, C₁₋₆ alkylamino or C₁₋₆ dialkylamino, any of the foregoing morpholine, thiomorpholine, piperidine, piperazine and pyrrolidine rings being optionally substituted with C₁₋₄ alkyl (especially methyl), and any of the foregoing aryl, heteroaryl, aryloxy or heteroaryl groups being optionally substituted with one or more substituents selected from halo, hydroxy, mercapto, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ alkoxy, C₂₋₆ alkenyloxy, C₂₋₆ alkynyloxy, halo(C₁₋₆)alkyl, halo(C₁₋₆)alkoxy, C₁₋₆ alkylthio, halo(C₁₋₆)alkylthio, hydroxy(C₁₋₆)alkyl, C₁₋₄ alkoxy(C₁₋₆)alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenoxy, benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato, isothiocyanato, nitro, —NR′″R″″, —NHCOR′″, —NHCONR′″R″″, —CONR′″R″″, —SO₂R′″, —OSO₂R′″, —COR′″, —CR′″═NR″″ or —N═CR′″R″″, in which R′″ and R″″ are independently hydrogen, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy, halo-(C₁₋₄)alkoxy, C₁₋₄ alkylthio, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenyl or benzyl, the phenyl and benzyl groups being optionally substituted with halogen, C₁₋₄ alkyl or C₁₋₄ alkoxy. Of particular interest are compounds where W and Z are both N and X and Y are both CH.

The invention includes a compound of the general formula (1) as defined immediately above except that: C₇ alkylene and C₃₋₇ alkenylene are excluded as chains formed by R³ and R⁴; the C₃₋₆ chain that R³ and R⁴ may form may only be optionally substituted with one or more methyl groups; thiomorpholine, thiomorpholine S-oxide, thiomorpholine S-dioxide and piperazine are excluded as rings that R³ and R⁴ may form; tri(C₁₋₄)alkylsilyl is excluded as a substituent of any alkyl, alkenyl, alkynyl or cycloalkyl group or moiety, and any morpholine, piperidine or pyrrolidine ring is unsubstituted.

In another aspect the invention provides a compound of the general formula (1) wherein

W and X, W and Z, X and Y or Y and Z are N and the other two are CR⁸; R³ is H, halo, C₁₋₄ alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkyl; R is halo; R¹ is halo, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl, C₁₋₈ alkoxy, C₁₋₈ alkylthio, aryl, aryloxy, arylthio, heteroaryl, heteroaryloxy, heteroarylthio, aryl(C₁₋₄)alkyl, aryl(C₁₋₄)alkoxy, heteroaryl(C₁₋₄)alkyl, heteroaryl(C₁₋₄)alkoxy, aryl(C₁₋₄)alkylthio, heteroaryl(C₁₋₄)alkylthio, morpholino, piperidino or pyrrolidino;

R² is NR³R⁴;

R³ is C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₂₋₄ alkenyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl or phenylamino in which the phenyl ring is optionally substituted with one, two or three substituents selected from halo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy and halo(C₁₋₄)alkoxy; and R⁴ is H, C₁₋₄ alkyl or amino, or R³ and R⁴ together form a C₄₋₆ alkylene chain optionally substituted with C₁₋₄ alkyl or C₁₋₄ alkoxy, or, together with the nitrogen atom to which they are attached, R³ and R⁴ form a morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or piperazine N—(C₁₋₄)alkyl (especially N-methyl) ring; any of the foregoing alkyl, alkenyl, alkynyl or cycloalkyl groups or moieties (other than for R⁸) being optionally substituted with halogen, cyano, C₁₋₆ alkoxy, C₁₋₆ alkylcarbonyl, C₁₋₆ alkoxycarbonyl, C₁₋₆ haloalkoxy, C₁₋₆ alkylthio, tri(C₁₋₄)alkylsilyl, C₁₋₆ alkylamino or C₁₋₆ dialkylamino, any of the foregoing morpholine, thiomorpholine, piperidine, piperazine and pyrrolidine rings being optionally substituted with C₁₋₄ alkyl (especially methyl), and any of the foregoing aryl or heteroaryl groups or moieties being optionally substituted with one or more substituents selected from halo, hydroxy, mercapto, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ alkoxy, C₂₋₆ alkenyloxy, C₂₋₆ alkynyloxy, halo(C₁₋₆)alkyl, halo(C₁₋₆)alkoxy, C₁₋₆ alkylthio, halo(C₁₋₆)alkylthio, hydroxy(C₁₋₆)alkyl, C₁₋₄ alkoxy(C₁₋₆)alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenoxy, benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato, isothiocyanato, nitro, —NR′″R″″, —NHCOR′″, —NHCONR′″R″″, —CONR′″R″″, —SO₂R′″, —OSO₂R′″, —COR′″, —CR′″═NR″″ or —N═CR′″R″″, in which R′″ and R″″ are independently hydrogen, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy, halo(C₁₋₄)alkoxy, C₁₋₄ alkylthio, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenyl or benzyl, the phenyl and benzyl groups being optionally substituted with halogen, C₁₋₄ alkyl or C₁₋₄ alkoxy. Of particular interest are compounds where W and Z are both N and X and Y are both CH.

The invention includes a compound of the general formula (1) as defined immediately above except that: the C₄₋₆ chain that R³ and R⁴ may form may only be optionally substituted with methyl; thiomorpholine, thiomorpholine S-oxide, thiomorpholine S-dioxide and piperazine are excluded as rings that R³ and R⁴ may form; tri(C₁₋₄)alkylsilyl is excluded as a substituent of any alkyl, alkenyl, alkynyl or cycloalkyl group or moiety, and any morpholine, piperidine or pyrrolidine ring is unsubstituted.

In yet another aspect the invention provides a compound of the general formula (1) wherein

W and X, W and Z, X and Y or Y and Z are N and the other two are CR³; R³ is H, halo, C₁₋₄ alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkyl; R is halo; R¹ is optionally substituted phenyl;

R² is NR³R⁴;

R³ and R⁴ are independently H, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, aryl, aryl(C₁₋₈)alkyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl, heteroaryl, heteroaryl(C₁₋₈)alkyl, NR⁵R⁶, provided that not both R³ and R⁴ are H or NR⁵R⁶, or R³ and K⁴ together form a C₃₋₇ alkylene or C₃₋₇ alkenylene chain optionally substituted with one or more C₁₋₄ alkyl or C₁₋₄ alkoxy groups, or, together with the nitrogen atom to which they are attached, R³ and R⁴ form a morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or piperazine N—(C₁₋₄)alkyl (especially N-methyl) ring; and R⁵ and R⁶ are independently H, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, aryl, aryl(C₁₋₈)alkyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl, heteroaryl or heteroaryl(C₁₋₈)alkyl; any of the foregoing alkyl, alkenyl, alkynyl or cycloalkyl groups or moieties (other than for R⁸) being optionally substituted with halogen, cyano, C₁₋₆ alkoxy, C₁₋₆ alkylcarbonyl, C₁₋₆ alkoxycarbonyl, C₁₋₆ haloalkoxy, C₁₋₆ alkylthio, tri(C₁₋₄)alkylsilyl, C₁₋₆ alkylamino or C₁₋₆ dialkylamino, any of the foregoing morpholine, thiomorpholine, piperidine, piperazine and pyrrolidine rings being optionally substituted with C₁₋₄ alkyl (especially methyl), and any of the foregoing aryl or heteroaryl groups or moieties, including the phenyl group of R¹, being optionally substituted with one or more substituents selected from halo, hydroxy, mercapto, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ alkoxy, C₂₋₆ alkenyloxy, C₂₋₆ alkynyloxy, halo(C₁₋₆)alkyl, halo(C₁₋₆)alkoxy, C₁₋₆ alkylthio, halo(C₁₋₆)alkylthio, hydroxy(C₁₋₆)alkyl, C₁₋₄ alkoxy(C₁₋₆)alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenoxy, benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato, isothiocyanato, nitro, —NR′″R″″, —NHCOR′″, —NHCONR′″R″″, —CONR′″R″″, —SO₂R′″, —OS₂R′″, —COR′″, —CR′″═NR″″ or —N═CR′″R″″, in which R′″ and R″″ are independently hydrogen, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy, halo(C₁₋₄)alkoxy, C₁₋₄ alkylthio, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenyl or benzyl, the phenyl and benzyl groups being optionally substituted with halogen, C₁₋₄ alkyl or C₁₋₄ alkoxy. Of particular interest are compounds where W and Z are both N and X and Y are both CH.

The invention includes a compound of the general formula (1) as defined immediately above except that: C₁₋₈ alkoxy and C₁₋₈ alkylthio are excluded as values of R and R²; C₇ alkylene and C₃₋₇ alkenylene are excluded as chains formed by R³ and R⁴; the C₃₋₆ chain that R³ and R⁴ may form may only be optionally substituted with one or more methyl groups; thiomorpholine, thiomorpholine S-oxide, thiomorpholine S-dioxide and piperazine are excluded as rings that R³ and R⁴ may form; tri(C₁₋₄)alkylsilyl is excluded as a substituent of any alkyl, alkenyl, alkynyl or cycloalkyl group or moiety, and the morpholine ring that R³ and R⁴ may form is unsubstituted.

In still yet another aspect the invention provides a compound of the general formula (1) wherein W and X, W and Z, X and Y or Y and Z are N and the other two are CR⁸;

R⁸ is H, halo(e.g. fluoro, chloro or bromo), C₁₋₄ alkyl (e.g. methyl), C₁₋₄ alkoxy (e.g. methoxy) or halo(C₁₋₄)alkyl (e.g. trifluoromethyl); R is halo (e.g. fluoro, chloro or bromo); R¹ is phenyl optionally substituted with from one to five halogen atoms or with from one to three substituents selected from halo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy or halo(C₁₋₄) alkoxy, pyridyl optionally substituted with from one to four halogen atoms or with from one to three substituents selected from halo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkoxy, 2- or 3-thienyl optionally substituted with from one to three halogen atoms or with from one to three substituents selected from halo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkoxy, or piperidino or morpholino both optionally substituted with one or two methyl groups;

R is NR³R⁴;

R³ is C₁₋₈ alkyl, halo(C₁₋₈)alkyl, hydroxy(C₁₋₈)alkyl, C₁₋₄ alkoxy(C₁₋₈)alkyl, C₁₋₄ alkoxyhalo-(C₁₋₈)alkyl, tri(C₁₋₄)alkylsilyl(C₁₋₆)alkyl, C₁₋₄ alkylcarbonyl(C₁₋₈)alkyl, C₁₋₄ alkylcarbonylhalo(C₁₋₈)alkyl, phenyl(1-4)alkyl, C₂₋₈ alkenyl, halo(C₂₋₈)alkenyl, C₂₋₈ alkynyl, C₃₋₈ cycloalkyl optionally substituted with chloro, fluoro or methyl, C₃₋₈ cycloalkyl(C₁₋₄)alkyl, phenylamino, piperidino or morpholino, the phenyl ring of phenylalkyl or phenylamino being optionally substituted with one, two or three substituents selected from halo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy and halo(C₁₋₄)alkoxy; and R⁴ is H, C₁₋₄ alkyl, halo(C₁₋₄)alkyl or amino, or R³ and R⁴ together form a C₃₋₇ alkylene or C₃₋₇ alkenylene chain optionally substituted with methyl, or, together with the nitrogen atom to which they are attached, R³ and R⁴ form a morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or piperazine N—(C₁₋₄)alkyl (especially N-methyl) ring, in which the morpholine or piperazine rings are optionally substituted with methyl. Of particular interest are compounds where W and Z are both N and X and Y are both CH.

In still yet another aspect the invention provides a compound of the general formula (1) wherein

W and X, W and Z, X and Y or Y and Z are N and the other two are CR⁸; R⁸ is H, halo, C₁₋₄ alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkyl; R is halo; R¹ is phenyl optionally substituted with from one to five halogen atoms or with from one to three substituents selected from halo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy or halo(C₁₋₄) alkoxy;

R² is NR³R⁴;

R³ is C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₂₋₄ alkenyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl or phenylamino in which the phenyl ring is optionally substituted with one, two or three substituents selected from halo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy and halo(C₁₋₄)alkoxy; and R⁴ is H, C₁₋₄ alkyl or amino, or R³ and R⁴ together form a C₄₋₆ alkylene chain optionally substituted with methyl, or, together with the nitrogen atom to which they are attached, R³ and R⁴ form a morpholine ring. Of particular interest are compounds where W and Z are both N and X and Y are both CH.

Compounds that form part of the invention are illustrated in Tables 1 to 127 below. Characterising data are given later in the Examples and in Table 133.

In Table 1 the compounds have the general formula (1A), where W and Z are N, X and Y are CH, R is Cl, R¹ is 2,4,6-trifluorophenyl and R³ and R⁴ are as shown in the table.

TABLE 1

Cmpd No R³ R⁴  1 C₂H₅ H  2 n-C₃H₇ H  3 i-C₃H₇ H  4 n-C₄H₉ H  5 t-C₄H₉ H  6 CH₂═CHCH₂ H  7 CH₂═C(CH₃)CH₂ H  8 CF₃CH₂ H  9 CF₃CH₂CH₂ H  10 CF₃CH₂CH₂CH₂ H  11 CF₃(CH₃)CH H  12 (S)-CF₃(CH₃)CH H  13 (R)-CF₃(CH₃)CH H  14 cyclo-C₃H₅ H  15 cyclo-C₄H₇ H  16 cyclo-C₅H₉ H  17 cyclo-C₆H₁₁ H  18 cyclo-C₃H₅CH₂ H  19 cyclo-C₄H₇CH₂ H  20 —(CH₂)₂O(CH₂)₂—  21 cyclo-C₆H₁₁CH₂ H  22 —(CH₂)₂CH(CH₃)(CH₂)₂—  23 CH₃CH₂(CH₃)CH H  24 (S)-CH₃CH₂(CH₃)CH H  25 (R)-CH₃CH₂(CH₃)CH H  26 C₂H₅ C₂H₅  27 n-C₃H₇ n-C₃H₇  28 CH₂═C(CH₃)CH₂ C₂H₅  29 CF₃CH₂ C₂H₅  30 C₂H₅ NH₂  31 n-C₃H₇ NH₂  32 i-C₃H₇ NH₂  33 n-C₄H₉ NH₂  34 CH₂═CHCH₂ NH₂  35 CH₂═C(CH₃)CH₂ NH₂  36 CF₂═CFCH₂CH₂ NH₂  37 CF₃CH₂ NH₂  38 CF₃CH₂CH₂ NH₂  39 CF₃CH₂CH₂CH₂ NH₂  40 4-t-C₄H₉-C₆H₄NH H  41 4-F—C₆H₄NH H  42 C₆H₅NH H  43 4-CH₃—C₆H₄NH H  44 4-Br—C₆H₄NH H  45 2-F—C₆H₄NH H  46 3,4-Cl₂—C₆H₃NH H  47 3-CF₃—C₆H₄NH H  48 3,5-Cl₂—C₆H₃NH H  49 4-CF₃O—C₆H₅NH H  50 2-CF₃—C₆H₄NH H  51 4-CF₃—C₆H₄NH H  52 2-Br—C₆H₄NH H  53 2-Cl—C₆H₄NH H  54 2-CH₃-4-Cl—C₆H₃NH H  55 2-CH₃-5-F—C₆H₃NH H  56 3-Cl—C₆H₄NH H  57 CH₃ H  58 (CH₃)₂CHCH₂ H  59 (CH₃)₃CCH₂ H  60 (CH₃)₃C(CH₃)CH H  61 CH₃CH₂(CH₃)₂C H  62 CH₃CH₂(CF₃)CH H  63 (S)-CH₃CH₂(CF₃)CH H  64 (R)-CH₃CH₂(CF₃)CH H  65 CH₃CH₂(CH₃CH₂)CH H  66 (CH₃)₂CH(CH₃CH₂)CH H  67 (CH₃)₂CH(CH₃)CH H  68 (CH₃)₂CH(CF₃)CH H  69 (S)-(CH₃)₂CH(CF₃)CH H  70 (R)-(CH₃)₂CH(CF₃)CH H  71 HC═C(CH₃)CH₂ H  72 CH₂═CH(CH₃CH₂)CH H  73 CH₃CH₂CH₂(CH₃)CH H  74 CH₃CH₂CH₂(CF₃)CH H  75 (S)-CH₃CH₂CH₂(CF₃)CH H  76 (R)-CH₃CH₂CH₂(CF₃)CH H  77 CH₃CH₂CH₂(CH₃)₂C H  78 CH₃CH₂(CH₃)CHCH₂ H  79 (CH₃)₂CHCH₂CH₂ H  80 (CH₃)₃CCH₂CH₂ H  81 CH₃CH₂(CH₃)CH(CH₃)—CH H  82 CH₃CH₂(CH₃)CH(CF₃)—CH H  83 (S)-CH₃CH₂(CH₃)CH—(CF₃)CH H  84 (R)-CH₃CH₂(CH₃)CH—(CF₃)CH H  85 CH₃(CH₃)CHCH₂(CH₃)—CH H  86 CH₃(CH₃)CHCH₂(CF₃)—CH H  87 (S)-CH₃(CH₃)CHCH₂—(CF₃)CH H  88 (R)-CH₃(CH₃)CHCH₂—(CF₃)CH H  89 (CH₃)₂CH(CH₃)CH—(CH₃)CH₂ H  90 (CH₃)₃CCH₂(CH₃)CH H  91 E-CH₃CH═CH(CH₃)CH H  92 E-CH₃CH═CH(CH₃CH₂)—CH H  93 CH₃CH₂CH₂(CH₃CH₂)—CH H  94 CH₃CH₂(CH₃CH₂)—CHCH₂ H  95 CF₂═CFCH₂CH₂ H  96 CF₃CH₂(CH₃)CHCH₂ H  97 CF₃CF₂CH₂CH₂ H  98 CF₃CF₂CF₂CH₂ H  99 CF₂═C(CH₃)CH₂CH₂ H 100 CH₃CH₂CH₂CH₂CH₂ H 101 CH₃CH₂CH₂CH₂—(CH₃)CH H 102 CH₃CH₂CH₂(CH₃)—CHCH₂ H 103 CH₃CH₂(CH₃)CHCH₂₋CH₂ H 104 CH₃CH₂CH₂(CH₃)CH—(CH₃)CH H 105 CH₃CH₂(CH₃)CHCH₂₋(CH₃)CH H 106 HOCH₂CH₂ H 107 CH₃OCH₂CH₂ H 108 CH₃OCH₂(CH₃)CH H 109 CH₃OCH₂(CF₃)CH H 110 CH₃OCH₂(CH₃)₂C H 111 CH₃O(CH₃)CHCH₂ H 112 CH₃O(CH₃)CH(CH₃)CH H 113 HC≡CCH₂ H 114 CH₃C≡CCH₂ H 115 HC≡CCH₂CH₂ H 116 HOCH₂CH₂CH₂ H 117 CH₃OCH₂CH₂CH₂ H 118 (CH₃)₃SiCH₂ H 119 C₆H₅CH₂ H 120 C₆H₅(CH₃)CH H 121 4-F—C₆H₄CH₂ H 122 4-Cl—C₆H₄CH₂ H 123 4-F—C₆H₅(CH₃)CH H 124 4-Cl—C₆H₅(CH₃)CH H 125 C₆H₅CH₂CH₂ H 126 4-F—C₆H₅CH₂CH₂ H 127 1-piperidino H 128 1-pyrrolidino H 129 cyclo-C₅H₉CH₂ H 130 Bicyclo[2.2.1]hept-2-yl H 131 1-CH₃-cyclopropyl H 132 cis-2-CH₃-cyclopropyl H 133 trans-2-CH₃-cyclopropyl H 134 2,2-(CH₃)₂-cyclopropyl H 135 1-CH₃-cyclobutyl H 136 cis-2-CH₃-cyclobutyl H 137 trans-2-CH₃-cyclobutyl H 138 cis-3-CH₃-cyclobutyl H 139 trans-3-CH₃-cyclobutyl H 140 2,2-(CH₃)₂-cyclobutyl H 141 3,3-(CH₃)₂-cyclobutyl H 142 1-CH₃-cyclopentyl H 143 cis-2-CH₃-cyclopentyl H 144 trans-2-CH₃-cyclopentyl H 145 cis-3-CH₃-cyclopentyl H 146 trans-3-CH₃-cyclopentyl H 147 2,2-(CH₃)₂-cyclopentyl H 148 3,3-(CH₃)₂-cyclopentyl H 149 1-CH₃-cyclohexyl H 150 cis-2-CH₃-cyclohexyl H 151 trans-2-CH₃-cyclohexyl H 152 cis-3-CH₃-cyclohexyl H 153 trans-3-CH₃-cyclohexyl H 154 2,2-(CH₃)₂-cyclohexyl H 155 3,3-(CH₃)₂-cyclohexyl H 156 cis-4-CH₃-cyclohexyl H 157 trans-4-CH₃-cyclohexyl H 158 4,4-(CH₃)₂-cyclohexyl H 159 4-(CH₃)₃C-cyclohexyl H 160 —(CH₂)₃— 161 —(CH₂)₄— 162 —(CH₂)₅— 163 —(CH₂)₆— 164 —(CH₂)₂(CH₃)₂C(CH₂)₂— 165 —(CH₃)CH(CH₂)₂— 166 —(CH₃)CH(CH₂)₃— 167 —(CH₃)CH(CH₂)₄— 168 —(CH₃)CH(CH₂)₅— 169 —CH₂CH═CH(CH₂)₂— 170 —(CH₂)₂NH(CH₂)₂— 171 —(CH₂)₂NCH₃(CH₂)₂— 172 —(CH₂)₂S(CH₂)₂— 173 —(CH₂)₂SO(CH₂)₂— 174 —(CH₂)₂SO₂(CH₂)₂— 175 —CH₂(CH₃)CHO(CH₃)CHCH₂— 176 C₂H₅ CH₃ 177 n-C₃H₇ CH₃ 178 i-C₃H₇ CH₃ 179 n-C₄H₉ CH₃ 180 t-C₄H₉ CH₃ 181 CH₂═CHCH₂ CH₃ 182 CH₂═C(CH₃)CH₂ CH₃ 183 CF₃CH₂ CH₃ 184 CF₃CH₂CH₂ CH₃ 185 CF₃CH₂CH₂CH₂ CH₃ 186 CF₃(CH₃)CH CH₃ 187 (S)-CF₃(CH₃)CH CH₃ 188 (R)-CF₃(CH₃)CH CH₃ 189 cyclo-C₃H₅ CH₃ 190 cyclo-C₄H₇ CH₃ 191 cyclo-C₅H₉ CH₃ 192 cyclo-C₆H₁₁ CH₃ 193 cyclo-C₃H₅CH₂ CH₃ 194 cyclo-C₄H₇CH₂ CH₃ 195 cyclo-C₆H₁₁CH₂ CH₃ 196 CH₃CH₂(CH₃)CH CH₃ 197 (S)-CH₃CH₂(CH₃)CH CH₃ 198 (R)-CH₃CH₂(CH₃)CH CH₃ 199 cyclo-C₇H₁₃ CH₃ 200 CH₂═C(CH₃)CH₂ CH₃ 201 CF₃CH₂ CH₃ 202 4-t-C₄H₉—C₆H₄NH CH₃ 203 4-F-C₆H₄NH CH₃ 204 C₆H₅NH CH₃ 205 4-CH₃—C₆H₄NH CH₃ 206 4-Br—C₆H₄NH CH₃ 207 2-F-C₆H₄NH CH₃ 208 3,4-Cl₂—C₆H₃NH CH₃ 209 3-CF₃—C₆H₄NH CH₃ 210 3,5-Cl₂—C₆H₃NH CH₃ 211 4-CF₃O—C₆H₅NH CH₃ 212 2-CF₃—C₆H₄NH CH₃ 213 4-CF₃—C₆H₄NH CH₃ 214 2-Br—C₆H₄NH CH₃ 215 2-Cl—C₆H₄NH CH₃ 216 2-CH₃-4-Cl—C₆H₃NH CH₃ 217 2-CH₃-5-F—C₆H₃NH CH₃ 218 3-Cl—C₆H₄NH CH₃ 219 CH₃ CH₃ 220 (CH₃)₂CHCH₂ CH₃ 221 (CH₃)₃CCH₂ CH₃ 222 (CH₃)₃C(CH₃)CH CH₃ 223 CH₃CH₂(CH₃)₂C CH₃ 224 CH₃CH₂(CF₃)CH CH₃ 225 (S)-CH₃CH₂(CF₃)CH CH₃ 226 (R)-CH₃CH₂(CF₃)CH CH₃ 227 CH₃CH₂(CH₃CH₂)CH CH₃ 228 (CH₃)₂CH(CH₃CH₂)CH CH₃ 229 (CH₃)₂CH(CH₃)CH CH₃ 230 (CH₃)₂CH(CF₃)CH CH₃ 231 (S)-(CH₃)₂CH(CF₃)CH CH₃ 232 (R)-(CH₃)₂CH(CF₃)CH CH₃ 233 HC═C(CH₃)CH₂ CH₃ 234 CH₂═CH(CH₃CH₂)CH CH₃ 235 CH₃CH₂CH₂(CH₃)CH CH₃ 236 CH₃CH₂CH₂(CF₃)CH CH₃ 237 (S)-CH₃CH₂CH₂(CF₃)CH CH₃ 238 (R)-CH₃CH₂CH₂(CF₃)CH CH₃ 239 CH₃CH₂CH₂(CF₃)₂C CH₃ 240 CH₃CH₂(CH₃)CHCH₂ CH₃ 241 (CH₃)₂CHCH₂CH₂ CH₃ 242 (CH₃)₃CCH₂CH₂ CH₃ 243 CH₃CH₂(CH₃)CH(CH₃)—CH CH₃ 244 CH₃CH₂(CH₃)CH(CF₃)—CH CH₃ 245 (S)-CH₃CH₂(CH₃)CH—(CF₃)CH CH₃ 246 (R)-CH₃CH₂(CH₃)CH—(CF₃)CH CH₃ 247 CH₃(CH₃)CHCH₂—(CH₃)CH CH₃ 248 CH₃(CH₃)CHCH₂—(CF₃)CH CH₃ 249 (S)-CH₃(CH₃)CHCH₂—(CF₃)CH CH₃ 250 (R)-CH₃(CH₃)HCH₂—(CF₃)CH CH₃ 251 (CH₃)₂CH(CH₃)CH(CH₃)—CH₂ CH₃ 252 (CH₃)₃CCH₂(CH₃)CH CH₃ 253 E-CH₃CH═CH(CH₃)CH CH₃ 254 E-CH₃CH═CH(CH₃CH₂)—CH CH₃ 255 CH₃CH₂CH₂(CH₃CH₂)—CH CH₃ 256 CH₃CH₂(CH₃CH₂)—CHCH₂ CH₃ 257 CF₂═CFCH₂CH₂ CH₃ 258 CF₃CH₂(CH₃)CHCH₂ CH₃ 259 CF₃CF₂CH₂CH₂ CH₃ 260 CF₃CF₂CF₂CH₂ CH₃ 261 CF₂═C(CH₃)CH₂CH₂ CH₃ 262 CH₃CH₂CH₂CH₂CH₂ CH₃ 263 CH₃CH₂CH₂CH₂(CH₃)—CH CH₃ 264 CH₃CH₂CH₂(CH₃)—CHCH₂ CH₃ 265 CH₃CH₂(CH₃)CHCH₂—CH₂ CH₃ 266 CH₃CH₂CH₂(CH₃)CH—(CH₃)CH CH₃ 267 CH₃CH₂(CH₃)CHCH₂—(CH₃)CH CH₃ 268 HOCH₂CH₂ CH₃ 269 CH₃OCH₂CH₂ CH₃ 270 CH₃OCH₂(CH₃)CH CH₃ 271 CH₃OCH₂(CF₃)CH CH₃ 272 CH₃OCH₂(CH₃)₂C CH₃ 273 CH₃O(CH₃)CHCH₂ CH₃ 274 CH₃O(CH₃)CH(CH₃)CH CH₃ 275 HC≡CCH₂ CH₃ 276 CH₃C≡CCH₂ CH₃ 277 HC≡CCH₂CH₂ CH₃ 278 HOCH₂CH₂CH₂ CH₃ 279 CH₃OCH₂CH₂CH₂ CH₃ 280 (CH₃)₃SiCH₂ CH₃ 281 C₆H₅CH₂ CH₃ 282 C₆H₅(CH₃)CH CH₃ 283 4-F—C₆H₄CH₂ H 284 4-Cl—C₆H₄CH₂ CH₃ 285 4-F—C₆H₅(CH₃)CH CH₃ 286 4-Cl—C₆H₅(CH₃)CH CH₃ 287 C₆H₅CH₂CH₂ CH₃ 288 4-F—C₆H₅CH₂CH₂ CH₃ 289 1-piperidino CH₃ 290 1-pyrrolidino CH₃ 291 cyclo-C₅H₉CH₂ CH₃ 292 bicyclo[2.2.1]hept-2-yl CH₃ 293 1-CH₃-cyclopropyl CH₃ 294 cis-2-CH₃-cyclopropyl CH₃ 295 trans-2-CH₃-cyclopropyl CH₃ 296 2,2-(CH₃)₂-cyclopropyl CH₃ 297 1-CH₃-cyclobutyl CH₃ 298 cis-2-CH₃-cyclobutyl CH₃ 299 trans-2-CH₃-cyclobutyl CH₃ 300 cis-3-CH₃-cyclobutyl CH₃ 301 trans-3-CH₃-cyclobutyl CH₃ 302 2,2-(CH₃)₂-cyclobutyl CH₃ 303 3,3-(CH₃)₂-cyclobutyl CH₃ 304 1-CH₃-cyclopentyl CH₃ 305 cis-2-CH₃-cyclopentyl CH₃ 306 trans-2-CH₃-cyclopentyl CH₃ 307 cis-3-CH₃-cyclopentyl CH₃ 308 trans-3-CH₃-cyclopentyl CH₃ 309 2,2-(CH₃)₂-cyclopentyl CH₃ 310 3,3-(CH₃)₂-cyclopentyl CH₃ 311 1-CH₃-cyclohexyl CH₃ 312 cis-2-CH₃-cyclohexyl CH₃ 313 trans-2-CH₃-cyclohexyl CH₃ 314 cis-3-CH₃-cyclohexyl CH₃ 315 trans-3-CH₃-cyclohexyl CH₃ 316 2,2-(CH₃)₂-cyclohexyl CH₃ 317 3,3-(CH₃)₂-cyclohexyl CH₃ 318 cis-4-CH₃-cyclohexyl CH₃ 319 trans-4-CH₃-cyclohexyl CH₃ 320 4,4-(CH₃)₂-cyclohexyl CH₃ 321 4-(CH₃)₃C-cyclohexyl CH₃ 322 n-C₃H₇ C₂H₅ 323 i-C₃H₇ C₂H₅ 324 n-C₄H₉ C₂H₅ 325 t-C₄H₉ C₂H₅ 326 CH₂═CHCH₂ C₂H₅ 327 CF₃CH₂CH₂ C₂H₅ 328 CF₃CH₂CH₂CH₂ C₂H₅ 329 CF₃(CH₃)CH C₂H₅ 330 (S)-CF₃(CH₃)CH C₂H₅ 331 (R)-CF₃(CH₃)CH C₂H₅ 332 cyclo-C₃H₅ C₂H₅ 333 cyclo-C₄H₇ C₂H₅ 334 cyclo-C₅H₉ C₂H₅ 335 cyclo-C₆H₁₁ C₂H₅ 336 cyclo-C₃H₅CH₂ C₂H₅ 337 cyclo-C₄H₇CH₂ C₂H₅ 338 cyclo-C₆H₁₁CH₂ C₂H₅ 339 CH₃CH₂(CH₃)CH C₂H₅ 340 (S)-CH₃CH₂(CH₃)CH C₂H₅ 341 (R)-CH₃CH₂(CH₃)CH C₂H₅ 342 cyclo-C₇H₁₃ C₂H₅ 343 4-t-C₄H₉—C₆H₄NH C₂H₅ 344 4-F—C₆H₄NH C₂H₅ 345 C₆H₅NH C₂H₅ 346 4-CH₃—C₆H₄NH C₂H₅ 347 4-Br—C₆H₄NH C₂H₅ 348 2-F—C₆H₄NH C₂H₅ 349 3,4-Cl₂—C₆H₃NH C₂H₅ 350 3-CF₃—C₆H₄NH C₂H₅ 351 3,5-Cl₂—C₆H₃NH C₂H₅ 352 4-CF₃O—C₆H₅NH C₂H₅ 353 2-CF₃—C₆H₄NH C₂H₅ 354 4-CF₃—C₆H₄NH C₂H₅ 355 2-Br—C₆H₄NH C₂H₅ 356 2-Cl—C₆H₄NH C₂H₅ 357 2-CH₃-4-Cl—C₆H₃NH C₂H₅ 358 2-CH₃-5-F—C₆H₃NH C₂H₅ 359 3-Cl—C₆H₄NH C₂H₅ 360 (CH₃)₂CHCH₂ C₂H₅ 361 (CH₃)₃CCH₂ C₂H₅ 362 (CH₃)₃C(CH₃)CH C₂H₅ 363 CH₃CH₂(CH₃)₂C C₂H₅ 364 CH₃CH₂(CF₃)CH C₂H₅ 365 (S)-CH₃CH₂(CF₃)CH C₂H₅ 366 (R)-CH₃CH₂(CF₃)CH C₂H₅ 367 CH₃CH₂(CH₃CH₂)CH C₂H₅ 368 (CH₃)₂CH(CH₃CH₂)CH C₂H₅ 369 (CH₃)₂CH(CH₃)CH C₂H₅ 370 (CH₃)₂CH(CF₃)CH C₂H₅ 371 (S)-(CH₃)₂CH(CF₃)CH C₂H₅ 372 (R)-(CH₃)₂CH(CF₃)CH C₂H₅ 373 HC═C(CH₃)CH₂ C₂H₅ 374 CH₂═CH(CH₃CH₂)CH C₂H₅ 375 CH₃CH₂CH₂(CH₃)CH C₂H₅ 376 CH₃CH₂CH₂(CF₃)CH C₂H₅ 377 (S)-CH₃CH₂CH₂(CF₃)CH C₂H₅ 378 (R)-CH₃CH₂CH₂(CF₃)CH C₂H₅ 379 CH₃CH₂CH₂(CH₃)₂C C₂H₅ 380 CH₃CH₂(CH₃)CHCH₂ C₂H₅ 381 (CH₃)₂CHCH₂CH₂ C₂H₅ 382 (CH₃)₃CCH₂CH₂ C₂H₅ 383 CH₃CH₂(CH₃)CH(CH₃)—CH C₂H₅ 384 CH₃CH₂(CH₃)CH(CF₃)—CH C₂H₅ 385 (S)-CH₃CH₂(CH₃)CH—(CF₃)CH C₂H₅ 386 (R)-CH₃CH₂(CH₃)CH—(CF₃)CH C₂H₅ 387 CH₃(CH₃)CHCH₂(CH₃)—CH C₂H₅ 388 CH₃(CH₃)CHCH₂(CF₃)—CH C₂H₅ 389 (S)-CH₃(CH₃)CHCH₂₋(CF₃)CH C₂H₅ 390 (R)-CH₃(CH₃)CHCH₂₋(CF₃)CH C₂H₅ 391 (CH₃)₂CH(CH₃)CH—(CH₃)CH₂ C₂H₅ 392 (CH₃)₃CCH₂(CH₃)CH C₂H₅ 393 E-CH₃CH═CH(CH₃)CH C₂H₅ 394 E-C H₃CH═CH—(CH₃CH₂)CH C₂H₅ 395 CH₃CH₂CH₂(CH₃CH₂)—CH C₂H₅ 396 CH₃CH₂(CH₃CH₂)CH—CH₂ C₂H₅ 397 CF₂═CFCH₂CH₂ C₂H₅ 398 CF₃CH₂(CH₃)CHCH₂ C₂H₅ 399 CF₃CF₂CH₂CH₂ C₂H₅ 400 CF₃CF₂CF₂CH₂ C₂H₅ 401 CF₂═C(CH₃)CH₂CH₂ C₂H₅ 402 CH₃CH₂CH₂CH₂CH₂ C₂H₅ 403 CH₃CH₂CH₂CH₂(CH₃)—CH C₂H₅ 404 CH₃CH₂CH₂(CH₃)CH—CH₂ C₂H₅ 405 CH₃CH₂(CH₃)CHCH₂—CH₂ C₂H₅ 406 CH₃CH₂CH₂(CH₃)CH—(CH₃)CH C₂H₅ 407 CH₃CH₂(CH₃)CHCH₂—(CH₃)CH C₂H₅ 408 HOCH₂CH₂ C₂H₅ 409 CH₃OCH₂CH₂ C₂H₅ 410 CH₃OCH₂(CH₃)CH C₂H₅ 411 CH₃OCH₂(CF₃)CH C₂H₅ 412 CH₃OCH₂(CH₃)₂C C₂H₅ 413 CH₃O(CH₃)CHCH₂ C₂H₅ 414 CH₃O(CH₃)CH(CH₃)CH C₂H₅ 415 HC≡CCH₂ C₂H₅ 416 CH₃C≡CCH₂ C₂H₅ 417 HC≡CCH₂CH₂ C₂H₅ 418 HOCH₂CH₂CH₂ C₂H₅ 419 CH₃OCH₂CH₂CH₂ C₂H₅ 420 (CH₃)₃SiCH₂ C₂H₅ 421 C₆H₅CH₂ C₂H₅ 422 C₆H₅(CH₃)CH C₂H₅ 423 4-F—C₆H₄CH₂ C₂H₅ 424 4-Cl—C₆H₄CH₂ C₂H₅ 425 4-F—C₆H₅(CH₃)CH C₂H₅ 426 4-Cl—C₆H₅(CH₃)CH C₂H₅ 427 C₆H₅CH₂CH₂ C₂H₅ 428 4-F—C₆H₅CH₂CH₂ C₂H₅ 429 1-piperidino C₂H₅ 430 1-pyrrolidino C₂H₅ 431 cyclo-C₅H₉CH₂ C₂H₅ 432 Bicyclo[2.2.1]hept-2-yl C₂H₅ 433 1-CH₃-cyclopropyl C₂H₅ 434 cis-2-CH₃-cyclopropyl C₂H₅ 435 trans-2-CH₃-cyclopropyl C₂H₅ 436 2,2-(CH₃)₂-cyclopropyl C₂H₅ 437 1-CH₃-cyclobutyl C₂H₅ 438 cis-2-CH₃-cyclobutyl C₂H₅ 439 trans-2-CH₃-cyclobutyl C₂H₅ 440 cis-3-CH₃-cyclobutyl C₂H₅ 441 trans-3-CH₃-cyclobutyl C₂H₅ 442 2,2-(CH₃)₂-cyclobutyl C₂H₅ 443 3,3-(CH₃)₂-cyclobutyl C₂H₅ 444 1-CH₃-cyclopentyl C₂H₅ 445 cis-2-CH₃-cyclopentyl C₂H₅ 446 trans-2-CH₃-cyclopentyl C₂H₅ 447 cis-3-CH₃-cyclopentyl C₂H₅ 448 trans-3-CH₃-cyclopentyl C₂H₅ 449 2,2-(CH₃)₂-cyclopentyl C₂H₅ 450 3,3-(CH₃)₂-cyclopentyl C₂H₅ 451 1-CH₃-cyclohexyl C₂H₅ 452 cis-2-CH₃-cyclohexyl C₂H₅ 453 trans-2-CH₃-cyclohexyl C₂H₅ 454 cis-3-CH₃-cyclohexyl C₂H₅ 355 trans-3-CH₃-cyclohexyl C₂H₅ 456 2,2-(CH₃)₂-cyclohexyl C₂H₅ 457 3,3-(CH₃)₂-cyclohexyl C₂H₅ 458 cis-4-CH₃-cyclohexyl C₂H₅ 459 trans-4-CH₃-cyclohexyl C₂H₅ 460 4,4-(CH₃)₂-cyclohexyl C₂H₅ 461 4-(CH₃)₃C-cyclohexyl C₂H₅ 462 n-C₃H₇ CF₃CH₂ 463 i-C₃H₇ CF₃CH₂ 464 n-C₄H₉ CF₃CH₂ 465 t-C₄H₉ CF₃CH₂ 466 CH₂═CHCH₂ CF₃CH₂ 467 CH₂═C(CH₃)CH₂ CF₃CH₂ 468 CF₃CH₂ CF₃CH₂ 469 CF₃CH₂CH₂ CF₃CH₂ 470 CF₃CH₂CH₂CH₂ CF₃CH₂ 471 CF₃(CH₃)CH CF₃CH₂ 472 (S)-CF₃(CH₃)CH CF₃CH₂ 473 (R)-CF₃(CH₃)CH CF₃CH₂ 474 cyclo-C₃H₅ CF₃CH₂ 475 cyclo-C₄H₇ CF₃CH₂ 476 cyclo-C₅H₉ CF₃CH₂ 477 cyclo-C₆H₁₁ CF₃CH₂ 478 cyclo-C₃H₅CH₂ CF₃CH₂ 479 cyclo-C₄H₇CH₂ CF₃CH₂ 480 cyclo-C₆H₁₁CH₂ CF₃CH₂ 481 CH₃CH₂(CH₃)CH CF₃CH₂ 482 (S)-CH₃CH₂(CH₃)CH CF₃CH₂ 483 (R)-CH₃CH₂(CH₃)CH CF₃CH₂ 484 cyclo-C₇H₁₃ CF₃CH₂ 485 CH₂═C(CH₃)CH₂ CF₃CH₂ 486 CF₃CH₂ CF₃CH₂ 487 4-t-C₄H₉—C₆H₄NH CF₃CH₂ 488 4-F—C₆H₄NH CF₃CH₂ 489 C₆H₅NH CF₃CH₂ 490 4-CH₃—C₆H₄NH CF₃CH₂ 491 4-Br—C₆H₄NH CF₃CH₂ 492 2-F—C₆H₄NH CF₃CH₂ 493 3,4-Cl₂—C₆H₃NH CF₃CH₂ 494 3-CF₃—C₆H₄NH CF₃CH₂ 495 3,5-Cl₂—C₆H₃NH CF₃CH₂ 496 4-CF₃O—C₆H₅NH CF₃CH₂ 497 2-CF₃—C₆H₄NH CF₃CH₂ 498 4-CF₃—C₆H₄NH CF₃CH₂ 499 2-Br—C₆H₄NH CF₃CH₂ 500 2-Cl—C₆H₄NH CF₃CH₂ 501 2-CH₃-4-Cl—C₆H₃NH CF₃CH₂ 502 2-CH₃-5-F—C₆H₃NH CF₃CH₂ 503 3-Cl—C₆H₄NH CF₃CH₂ 504 (CH₃)₂CHCH₂ CF₃CH₂ 505 (CH₃)₃CCH₂ CF₃CH₂ 506 (CH₃)₃C(CH₃)CH CF₃CH₂ 507 CH₃CH₂(CH₃)₂C CF₃CH₂ 508 CH₃CH₂(CF₃)CH CF₃CH₂ 509 (S)-CH₃CH₂(CF₃)CH CF₃CH₂ 510 (R)-CH₃CH₂(CF₃)CH CF₃CH₂ 511 CH₃CH₂(CH₃CH₂)CH CF₃CH₂ 512 (CH₃)₂CH(CH₃CH₂)CH CF₃CH₂ 513 (CH₃)₂CH(CH₃)CH CF₃CH₂ 514 (CH₃)₂CH(CF₃)CH CF₃CH₂ 515 (S)-(CH₃)₂CH(CF₃)CH CF₃CH₂ 516 (R)-(CH₃)₂CH(CF₃)CH CF₃CH₂ 517 HC═C(CH₃)CH₂ CF₃CH₂ 518 CH₂═CH(CH₃CH₂)CH CF₃CH₂ 520 CH₃CH₂CH₂(CH₃)CH CF₃CH₂ 521 CH₃CH₂CH₂(CF₃)CH CF₃CH₂ 522 (S)-CH₃CH₂CH₂(CF₃)CH CF₃CH₂ 523 (R)-CH₃CH₂CH₂(CF₃)CH CF₃CH₂ 524 CH₃CH₂CH₂(CH₃)₂C CF₃CH₂ 525 CH₃CH₂(CH₃)CHCH₂ CF₃CH₂ 526 (CH₃)₂CHCH₂CH₂ CF₃CH₂ 527 (CH₃)₃CCH₂CH₂ CF₃CH₂ 528 CH₃CH₂(CH₃)CH(CH₃)—CH CF₃CH₂ 529 CH₃CH₂(CH₃)CH(CF₃)—CH CF₃CH₂ 530 (S)-CH₃CH₂(CH₃)CH—(CF₃)CH CF₃CH₂ 531 (R)-CH₃CH₂(CH₃)CH—(CF₃)CH CF₃CH₂ 532 CH₃(CH₃)CHCH₂(CH₃)—CH CF₃CH₂ 533 CH₃(CH₃)CHCH₂(CF₃)—CH CF₃CH₂ 534 (S)-CH₃(CH₃)CHCH₂(CF₃)CH CF₃CH₂ 535 (R)-CH₃(CH₃)CHCH₂—(CF₃)CH CF₃CH₂ 536 (CH₃)₂CH(CH₃)CH—(CH₃)CH₂ CF₃CH₂ 537 (CH₃)₃CCH₂(CH₃)CH CF₃CH₂ 538 E-CH₃CH═CH(CH₃)CH CF₃CH₂ 539 E-CH₃CH═CH(CH₃CH₂)—CH CF₃CH₂ 540 CH₃CH₂CH₂(CH₃CH₂)—CH CF₃CH₂ 541 CH₃CH₂(CH₃CH₂)CH—CH₂ CF₃CH₂ 542 CF₂═CFCH₂CH₂ CF₃CH₂ 543 CF₃CH₂(CH₃)CHCH₂ CF₃CH₂ 544 CF₃CF₂CH₂CH₂ CF₃CH₂ 545 CF₃CF₂CF₂CH₂ CF₃CH₂ 546 CF₂═C(CH₃)CH₂CH₂ CF₃CH₂ 547 CH₃CH₂CH₂CH₂CH₂ CF₃CH₂ 548 CH₃CH₂CH₂CH₂(CH₃)—CH CF₃CH₂ 549 CH₃CH₂CH₂(CH₃)CH—CH₂ CF₃CH₂ 550 CH₃CH₂(CH₃)CHCH₂—CH₂ CF₃CH₂ 551 CH₃CH₂CH₂(CH₃)CH—(CH₃)CH CF₃CH₂ 552 CH₃CH₂(CH₃)CHCH₂—(CH₃)CH CF₃CH₂ 553 HOCH₂CH₂ CF₃CH₂ 554 CH₃OCH₂CH₂ CF₃CH₂ 555 CH₃OCH₂(CH₃)CH CF₃CH₂ 556 CH₃OCH₂(CF₃)CH CF₃CH₂ 557 CH₃OCH₂(CH₃)₂C CF₃CH₂ 558 CH₃O(CH₃)CHCH₂ CF₃CH₂ 559 CH₃O(CH₃)CH(CH₃)CH CF₃CH₂ 560 HC≡CCH₂ CF₃CH₂ 561 CH₃C≡CCH₂ CF₃CH₂ 562 HC≡CCH₂CH₂ CF₃CH₂ 563 HOCH₂CH₂CH₂ CF₃CH₂ 564 CH₃OCH₂CH₂CH₂ CF₃CH₂ 565 (CH₃)₃SiCH₂ CF₃CH₂ 566 C₆H₅CH₂ CF₃CH₂ 567 C₆H₅(CH₃)CH CF₃CH₂ 568 4-F—C₆H₄CH₂ CF₃CH₂ 569 4-Cl—C₆H₄CH₂ CF₃CH₂ 570 4-F—C₆H₅(CH₃)CH CF₃CH₂ 571 4-Cl—C₆H₅(CH₃)CH CF₃CH₂ 572 C₆H₅CH₂CH₂ CF₃CH₂ 573 4-F—C₆H₅CH₂CH₂ CF₃CH₂ 574 1-piperidino CF₃CH₂ 575 1-pyrrolidino CF₃CH₂ 576 cyclo-C₅H₉CH₂ CF₃CH₂ 577 bicyclo[2.2.1]hept-2-yl CF₃CH₂ 578 1-CH₃-cyclopropyl CF₃CH₂ 579 cis-2-CH₃-cyclopropyl CF₃CH₂ 580 trans-2-CH₃-cyclopropyl CF₃CH₂ 581 2,2-(CH₃)₂-cyclopropyl CF₃CH₂ 582 1-CH₃-cyclobutyl CF₃CH₂ 583 cis-2-CH₃-cyclobutyl CF₃CH₂ 584 trans-2-CH₃-cyclobutyl CF₃CH₂ 585 cis-3-CH₃-cyclobutyl CF₃CH₂ 586 trans-3-CH₃-cyclobutyl CF₃CH₂ 587 2,2-(CH₃)₂-cyclobutyl CF₃CH₂ 588 3,3-(CH₃)₂-cyclobutyl CF₃CH₂ 589 1-CH₃-cyclopentyl CF₃CH₂ 590 cis-2-CH₃-cyclopentyl CF₃CH₂ 591 trans-2-CH₃-cyclopentyl CF₃CH₂ 592 cis-3-CH₃-cyclopentyl CF₃CH₂ 593 trans-3-CH₃-cyclopentyl CF₃CH₂ 594 2,2-(CH₃)₂-cyclopentyl CF₃CH₂ 595 3,3-(CH₃)₂-cyclopentyl CF₃CH₂ 596 1-CH₃-cyclohexyl CF₃CH₂ 597 cis-2-CH₃-cyclohexyl CF₃CH₂ 598 trans-2-CH₃-cyclohexyl CF₃CH₂ 599 cis-3-CH₃-cyclohexyl CF₃CH₂ 600 trans-3-CH₃-cyclohexyl CF₃CH₂ 601 2,2-(CH₃)₂-cyclohexyl CF₃CH₂ 602 3,3-(CH₃)₂-cyclohexyl CF₃CH₂ 603 cis-4-CH₃-cyclohexyl CF₃CH₂ 604 trans-4-CH₃-cyclohexyl CF₃CH₂ 605 4,4-(CH₃)₂-cyclohexyl CF₃CH₂ 606 4-(CH₃)₃C-cyclohexyl CF₃CH₂ 607 cis-1-CH₃-2-fluoro-cyclopropyl H 608 trans-1-CH₃-2-fluoro-cyclopropyl H 609 1-CH₃-2,2-difluoro-cyclopropyl H 610 cis-1-CH₃-2-chloro-2-fluorocyclopropyl H 611 trans-1-CH₃-2-chloro-2-fluorocyclopropyl H 612 CH₃CO(CH₃)CH H 613 CH₃CH₂CO(CH₃)CH H 614 (CH₃)₂CHCO(CH₃)CH H 615 (CH₃)₃CCO(CH₃)CH H 616 CH₃CH₂CH₂CO(CH₃)CH H 617 CH₃CO(CF₃)CH H 618 CH₃CH₂CO(CF₃)CH H 619 CH₃CO(CH₃)₂C H 620 CH₃CH₂CO(CH₃)₂C H 621 cis-1-CH₃-2-fluoro-cyclopropyl CH₃ 622 trans-1-CH₃-2-fluoro-cyclopropyl CH₃ 623 1-CH₃-2,2-difluoro-cyclopropyl CH₃ 624 cis-1-CH₃-2-chloro-2-fluorocyclopropyl CH₃ 625 trans-1-CH₃-2-chloro-2-fluorocyclopropyl CH₃ 626 CH₃CO(CH₃)CH CH₃ 627 CH₃CH₂CO(CH₃)CH CH₃ 628 (CH₃)₂CHCO(CH₃)CH CH₃ 629 (CH₃)₃CCO(CH₃)CH CH₃ 630 CH₃CH₂CH₂CO(CH₃)CH CH₃ 631 CH₃CO(CF₃)CH CH₃ 632 CH₃CH₂CO(CF₃)CH CH₃ 633 CH₃CO(CH₃)₂C CH₃ 634 CH₃CH₂CO(CH₃)₂C CH₃ 635 cis-1-CH₃-2-fluoro-cyclopropyl C₂H₅ 636 trans-1-CH₃-2-fluoro-cyclopropyl C₂H₅ 637 1-CH₃-2,2-difluoro-cyclopropyl C₂H₅ 638 cis-1-CH₃-2-chloro-2-fluorocyclopropyl C₂H₅ 639 trans-1-CH₃-2-chloro-2-fluorocyclopropyl C₂H₅ 640 CH₃CO(CH₃)CH C₂H₅ 641 CH₃CH₂CO(CH₃)CH C₂H₅ 642 (CH₃)₂CHCO(CH₃)CH C₂H₅ 643 (CH₃)₃CCO(CH₃)CH C₂H₅ 644 CH₃CH₂CH₂CO(CH₃)CH C₂H₅ 645 CH₃CO(CF₃)CH C₂H₅ 646 CH₃CH₂CO(CF₃)CH C₂H₅ 647 CH₃CO(CH₃)₂C C₂H₅ 648 CH₃CH₂CO(CH₃)₂C C₂H₅ 649 cis-1-CH₃-2-fluoro-cyclopropyl CF₃CH₂ 650 trans-1-CH₃-2-fluoro-cyclopropyl CF₃CH₂ 651 1-CH₃-2,2-difluoro-cyclopropyl CF₃CH₂ 652 cis-1-CH₃-2-chloro-2-fluorocyclopropyl CF₃CH₂ 653 trans-1-CH₃-2-chloro-2-fluorocyclopropyl CF₃CH₂ 654 CH₃CO(CH₃)CH CF₃CH₂ 655 CH₃CH₂CO(CH₃)CH CF₃CH₂ 656 (CH₃)₂CHCO(CH₃)CH CF₃CH₂ 657 (CH₃)₃CCO(CH₃)CH CF₃CH₂ 658 CH₃CH₂CH₂CO(CH₃)CH CF₃CH₂ 659 CH₃CO(CF₃)CH CF₃CH₂ 660 CH₃CH₂CO(CF₃)CH CF₃CH₂ 661 CH₃CO(CH₃)₂C CF₃CH₂ 662 CH₃CH₂CO(CH₃)₂C CF₃CH₂

Table 2

Table 2 consists of 662 compounds of the general formula (1A), where W and Z are N, X and Y are CH, R is Cl, R¹ is 2,5,6-trifluorophenyl, and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1 of Table 2 is the same as compound 1 of Table 1 except that in compound 1 of Table 2, R¹ is 2,5,6-trifluorophenyl. Similarly, compounds 2 to 662 of Table 2 are the same as compounds 2 to 662 of Table 1 except that in the compounds of Table 2, R¹ is 2,5,6-trifluorophenyl.

Table 3

Table 3 consists of 662 compounds of the general formula (1A), where W and Z are N, X and Y are CH, R is Cl, R¹ is 2,3,4,5,6-pentafluorophenyl, and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1 of Table 3 is the same as compound 1 of Table 1 except that in compound 1 of Table 3, R¹ is 2,3,4,5,6-pentafluorophenyl. Similarly, compounds 2 to 662 of Table 3 are the same as compounds 2 to 662 of Table 1 except that in the compounds of Table 3, R¹ is 2,3,4,5,6-pentafluorophenyl.

Table 4

Table 4 consists of 662 compounds of the general formula (1A), where W and Z are N, X and Y are CH, R is Cl, R¹ is 2,6-difluoro-4-methoxyphenyl, and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1 of Table 4 is the same as compound 1 of Table 1 except that in compound 1 of Table 4, R¹ is 2,6-difluoro-4-methoxyphenyl. Similarly, compounds 2 to 662 of Table 4 are the same as compounds 2 to 662 of Table 1 except that in the compounds of Table 4, R¹ is 2,6-difluoro-4-methoxyphenyl.

Table 5

Table 5 consists of 662 compounds of the general formula (1A), where W and Z are N, X and Y are CH, R is Cl, R¹ is 2-fluoro-6-chlorophenyl, and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1 of Table 5 is the same as compound 1 of Table 1 except that in compound 1 of Table 5, R¹ is 2-fluoro-6-chlorophenyl. Similarly, compounds 2 to 662 of Table 5 are the same as compounds 2 to 662 of Table 1 except that in the compounds of Table 5, R¹ is 2-fluoro-6-chlorophenyl.

Table 11

Table 11 consists of 662 compounds of the general formula (1A), where W and X are N and Y and Z are CH, R is Cl, R¹ is 2,4,6-trifluorophenyl, and the values of R³ and K⁴ are as listed in Table 1. Thus, compound 1 of Table 11 is the same as compound 1 of Table 1 except that in compound 1 of Table 11, the compound has the general formula (1A) where W and X are N and Y and Z are CH. Similarly, compounds 2 to 662 of Table 11 are the same as compounds 2 to 662 of Table 1 except that in the compounds of Table 11, the compounds have the general formula (1A) where W and X are N and Y and Z are CH.

Table 12

Table 12 consists of 662 compounds of the general formula (1A), where W and X are N and Y and Z are CH, R is Cl, R¹ is 2,5,6-trifluorophenyl, and the values of R³ and K⁴ are as listed in Table 1. Thus, compound 1 of Table 12 is the same as compound 1 of Table 2 except that in compound 1 of Table 12, the compound has the general formula (1A) where W and X are N and Y and Z are CH. Similarly, compounds 2 to 662 of Table 12 are the same as compounds 2 to 662 of Table 2 except that in the compounds of Table 12, the compounds have the general formula (1A) where W and X are N and Y and Z are CH.

Table 13

Table 13 consists of 662 compounds of the general formula (1A), where W and X are N and Y and Z are CH, R is Cl, R¹ is 2,3,4,5,6-pentafluorophenyl, and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1 of Table 13 is the same as compound 1 of Table 3 except that in compound 1 of Table 13, the compound has the general formula (1A) where W and X are N and Y and Z are CH. Similarly, compounds 2 to 662 of Table 13 are the same as compounds 2 to 662 of Table 3 except that in the compounds of Table 13, the compounds have the general formula (1A) where W and X are N and Y and Z are CH.

Table 14

Table 14 consists of 662 compounds of the general formula (1A), where W and X are N and Y and Z are CH, R is Cl, R¹ is 2,6-difluoro-4-methoxyphenyl, and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1 of Table 14 is the same as compound 1 of Table 4 except that in compound 1 of Table 14, the compound has the general formula (1A) where W and X are N and Y and Z are CH. Similarly, compounds 2 to 662 of Table 14 are the same as compounds 2 to 662 of Table 4 except that in the compounds of Table 14, the compounds have the general formula (1A) where W and X are N and Y and Z are CH.

Table 15

Table 15 consists of 662 compounds of the general formula (1A), where W and X are N and Y and Z are CH, R is Cl, R¹ is 2-fluoro-6-chlorophenyl, and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1 of Table 15 is the same as compound 1 of Table 5 except that in compound 1 of Table 15, the compound has the general formula (1A) where W and X are N and Y and Z are CH. Similarly, compounds 2 to 662 of Table 15 are the same as compounds 2 to 662 of Table 5 except that in the compounds of Table 15, the compounds have the general formula (1A) where W and X are N and Y and Z are CH.

Table 21

Table 21 consists of 662 compounds of the general formula (1A), where W and Z are CH and X and Y are N, R is Cl, R¹ is 2,4,6-trifluorophenyl, and the values of R³ and K⁴ are as listed in Table 1. Thus, compound 1 of Table 21 is the same as compound 1 of Table 1 except that in compound 1 of Table 21, the compound has the general formula (1A) where W and Z are CH and X and Y are N. Similarly, compounds 2 to 662 of Table 21 are the same as compounds 2 to 662 of Table 1 except that in the compounds of Table 21, the compounds have the general formula (1A) where W and Z are CH and X and Y are N.

Table 22

Table 22 consists of 662 compounds of the general formula (1A), where W and Z are CH and X and Y are N, R is Cl, R¹ is 2,5,6-trifluorophenyl, and the values of R³ and K⁴ are as listed in Table 1. Thus, compound 1 of Table 22 is the same as compound 1 of Table 2 except that in compound 1 of Table 22, the compound has the general formula (1A) where W and Z are CH and X and Y are N. Similarly, compounds 2 to 662 of Table 22 are the same as compounds 2 to 662 of Table 2 except that in the compounds of Table 22, the compounds have the general formula (1A) where W and Z are CH and X and Y are N.

Table 23

Table 23 consists of 662 compounds of the general formula (1A), where W and Z are CH and X and Y are N, R is Cl, R¹ is 2,3,4,5,6-pentafluorophenyl, and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1 of Table 23 is the same as compound 1 of Table 3 except that in compound 1 of Table 23, the compound has the general formula (1A) where W and Z are CH and X and Y are N. Similarly, compounds 2 to 662 of Table 23 are the same as compounds 2 to 662 of Table 3 except that in the compounds of Table 23, the compounds have the general formula (1A) where W and Z are CH and X and Y are N.

Table 24

Table 24 consists of 662 compounds of the general formula (1A), where W and Z are CH and X and Y are N, R is Cl, R¹ is 2,6-difluoro-4-methoxyphenyl, and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1 of Table 24 is the same as compound 1 of Table 4 except that in compound 1 of Table 24, the compound has the general formula (1A) where W and Z are CH and X and Y are N. Similarly, compounds 2 to 662 of Table 24 are the same as compounds 2 to 662 of Table 4 except that in the compounds of Table 24, the compounds have the general formula (1A) where W and Z are CH and X and Y are N.

Table 25

Table 25 consists of 662 compounds of the general formula (1A), where W and Z are CH and X and Y are N, R is Cl, R¹ is 2-fluoro-6-chlorophenyl, and the values of R³ and K⁴ are as listed in Table 1. Thus, compound 1 of Table 25 is the same as compound 1 of Table 5 except that in compound 1 of Table 25, the compound has the general formula (1A) where W and Z are CH and X and Y are N. Similarly, compounds 2 to 662 of Table 25 are the same as compounds 2 to 662 of Table 5 except that in the compounds of Table 25, the compounds have the general formula (1A) where W and Z are CH and X and Y are N.

Table 26

Table 26 consists of 662 compounds of the general formula (1A), where W and X are CH and Y and Z are N, R is Cl, R¹ is 2,4,6-trifluorophenyl, and the values of R³ and K⁴ are as listed in Table 1. Thus, compound 1 of Table 26 is the same as compound 1 of Table 1 except that in compound 1 of Table 26, the compound has the general formula (1A) where W and X are CH and Y and Z are N. Similarly, compounds 2 to 662 of Table 26 are the same as compounds 2 to 662 of Table 1 except that in the compounds of Table 26, the compounds have the general formula (1A) where W and X are CH and Y and Z are N.

Table 27

Table 27 consists of 662 compounds of the general formula (1A), where W and X are CH and Y and Z are N, R is Cl, R¹ is 2,5,6-trifluorophenyl, and the values of R³ and K⁴ are as listed in Table 1. Thus, compound 1 of Table 27 is the same as compound 1 of Table 2 except that in compound 1 of Table 27, the compound has the general formula (1A) where W and X are CH and Y and Z are N. Similarly, compounds 2 to 662 of Table 27 are the same as compounds 2 to 662 of Table 2 except that in the compounds of Table 27, the compounds have the general formula (1A) where W and X are CH and Y and Z are N.

Table 28

Table 28 consists of 662 compounds of the general formula (1A), where W and X are CH and Y and Z are N, R is Cl, R¹ is 2,3,4,5,6-pentafluorophenyl, and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1 of Table 28 is the same as compound 1 of Table 3 except that in compound 1 of Table 28, the compound has the general formula (1A) where W and X are CH and Y and Z are N. Similarly, compounds 2 to 662 of Table 28 are the same as compounds 2 to 662 of Table 3 except that in the compounds of Table 28, the compounds have the general formula (1A) where W and X are CH and Y and Z are N.

Table 29

Table 29 consists of 662 compounds of the general formula (1A), where W and X are CH and Y and Z are N, R is Cl, R¹ is 2,6-difluoro-4-methoxyphenyl, and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1 of Table 29 is the same as compound 1 of Table 4 except that in compound 1 of Table 29, the compound has the general formula (1A) where W and X are CH and Y and Z are N. Similarly, compounds 2 to 662 of Table 29 are the same as compounds 2 to 662 of Table 4 except that in the compounds of Table 29, the compounds have the general formula (1A) where W and X are CH and Y and Z are N.

Table 30

Table 30 consists of 662 compounds of the general formula (1A), where W and X are CH and Y and Z are N, R is Cl, R¹ is 2-fluoro-6-chlorophenyl, and the values of R³ and K⁴ are as listed in Table 1. Thus, compound 1 of Table 30 is the same as compound 1 of Table 5 except that in compound 1 of Table 30, the compound has the general formula (1A) where W and X are CH and Y and Z are N. Similarly, compounds 2 to 662 of Table 30 are the same as compounds 2 to 662 of Table 5 except that in the compounds of Table 30, the compounds have the general formula (1A) where W and X are CH and Y and Z are N.

Table 31

Table 31 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 31 R¹ is 2,6-difluorophenyl instead of 2-fluoro-6-chlorophenyl.

Table 32

Table 32 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 32 R¹ is 2-fluorophenyl instead of 2-fluoro-6-chlorophenyl.

Table 33

Table 33 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 33 R¹ is 2,3,5,6-tetrafluorophenyl instead of 2-fluoro-6-chlorophenyl.

Table 34

Table 34 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 34 R¹ is 2-chloro-4,6-difluorophenyl instead of 2-fluoro-6-chlorophenyl.

Table 35

Table 35 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 35 R¹ is 2-chlorophenyl instead of 2-fluoro-6-chlorophenyl.

Table 36

Table 36 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 36 R¹ is 2,6-dichlorophenyl instead of 2-fluoro-6-chlorophenyl.

Table 37

Table 37 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 37 R¹ is 2,4-dichlorophenyl instead of 2-fluoro-6-chlorophenyl.

Table 38

Table 38 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 38 R¹ is 2,4,6-trichlorophenyl instead of 2-fluoro-6-chlorophenyl.

Table 39

Table 39 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 39 R¹ is 2,3,6-trichlorophenyl instead of 2-fluoro-6-chlorophenyl.

Table 40

Table 40 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 40 R¹ is pentachlorophenyl instead of 2-fluoro-6-chlorophenyl.

Table 41

Table 41 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 41 R¹ is 2-fluoro-4,6-dichlorophenyl instead of 2-fluoro-6-chlorophenyl.

Table 42

Table 42 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 42 R¹ is 4-fluoro-2,6-dichlorophenyl instead of 2-fluoro-6-chlorophenyl.

Table 43

Table 43 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 43 R¹ is 2-bromophenyl instead of 2-fluoro-6-chlorophenyl.

Table 44

Table 44 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 44 R¹ is 2-fluoro-6-bromophenyl instead of 2-fluoro-6-chlorophenyl.

Table 45

Table 45 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 45 R¹ is 2-bromo-4,6-difluorophenyl instead of 2-fluoro-6-chlorophenyl.

Table 46

Table 46 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 46 R¹ is 2-fluoro-6-methylphenyl instead of 2-fluoro-6-chlorophenyl.

Table 47

Table 47 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 47 R¹ is 2-chloro-6-methylphenyl instead of 2-fluoro-6-chlorophenyl.

Table 48

Table 48 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 48 R¹ is 2-methoxyphenyl instead of 2-fluoro-6-chlorophenyl.

Table 49

Table 49 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 49 R¹ is 2,6-dimethoxyphenyl instead of 2-fluoro-6-chlorophenyl.

Table 50

Table 50 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 50 R¹ is 2-fluoro-6-methoxyphenyl instead of 2-fluoro-6-chlorophenyl.

Table 51

Table 51 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 51 R¹ is 2-trifluoromethylphenyl instead of 2-fluoro-6-chlorophenyl.

Table 52

Table 52 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 52 R¹ is 2-fluoro-6-trifluoromethylphenyl instead of 2-fluoro-6-chlorophenyl.

Table 53

Table 53 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 53 R¹ is 2,6-di-(trifluoromethyl)phenyl instead of 2-fluoro-6-chlorophenyl.

Table 54

Table 54 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 54 R¹ is 2-chloro-6-trifluoromethylphenyl instead of 2-fluoro-6-chlorophenyl.

Table 55

Table 55 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 55 R¹ is 2,4-difluoro-6-trifluoromethylphenyl instead of 2-fluoro-6-chlorophenyl.

Table 56

Table 56 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 56 R¹ is 2,4-difluoro-6-methoxyphenyl instead of 2-fluoro-6-chlorophenyl.

Table 57

Table 57 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 57 R¹ is 2,4-difluoro-6-methylphenyl instead of 2-fluoro-6-chlorophenyl.

Table 58

Table 58 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 58 R¹ is 2,4-difluoropyrid-3-yl instead of 2-fluoro-6-chlorophenyl.

Table 59

Table 59 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 59 R¹ is 3,5-difluoropyrid-4-yl instead of 2-fluoro-6-chlorophenyl.

Table 60

Table 60 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 60 R¹ is tetrafluoropyrid-4-yl instead of 2-fluoro-6-chlorophenyl.

Table 61

Table 61 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 61 R¹ is 3-fluoropyrid-2-yl instead of 2-fluoro-6-chlorophenyl.

Table 62

Table 62 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 62 R¹ is 4-fluoropyrid-3-yl instead of 2-fluoro-6-chlorophenyl.

Table 63

Table 63 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 63 R¹ is 3-fluoropyrid-4-yl instead of 2-fluoro-6-chlorophenyl.

Table 64

Table 64 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 64 R¹ is 2-fluoropyrid-3-yl instead of 2-fluoro-6-chlorophenyl.

Table 65

Table 65 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 65 R¹ is 2,4,6-trifluoropyrid-3-yl instead of 2-fluoro-6-chlorophenyl.

Table 66

Table 66 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 66 R¹ is 3,5-difluoropyrid-2-yl instead of 2-fluoro-6-chlorophenyl.

Table 67

Table 67 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 67 R¹ is 2,6-difluoropyrid-3-yl instead of 2-fluoro-6-chlorophenyl.

Table 68

Table 68 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 68 R¹ is 2,4-difluoro-6-methoxypyrid-3-yl instead of 2-fluoro-6-chlorophenyl.

Table 69

Table 69 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 69 R¹ is 2-fluoro-4-chloropyrid-3-yl instead of 2-fluoro-6-chlorophenyl.

Table 70

Table 70 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 70 R¹ is 3-fluoro-5-chloropyrid-4-yl instead of 2-fluoro-6-chlorophenyl.

Table 71

Table 71 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 71 R¹ is 2-chloro-4-fluoropyrid-3-yl instead of 2-fluoro-6-chlorophenyl.

Table 72

Table 72 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 72 R¹ is 2,4-dichloropyrid-3-yl instead of 2-fluoro-6-chlorophenyl.

Table 73

Table 73 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 73 R¹ is 3-chloropyrid-2-yl instead of 2-fluoro-6-chlorophenyl.

Table 74

Table 74 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 74 R¹ is 4-chloropyrid-3-yl instead of 2-fluoro-6-chlorophenyl.

Table 75

Table 75 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 75 R¹ is 3-chloropyrid-4-yl instead of 2-fluoro-6-chlorophenyl.

Table 76

Table 76 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 76 R¹ is 2-chloropyrid-3-yl instead of 2-fluoro-6-chlorophenyl.

Table 77

Table 77 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 77 R¹ is 3-trifluoromethylpyrid-2-yl instead of 2-fluoro-6-chlorophenyl.

Table 78

Table 78 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 78 R¹ is 4-trifluoromethylpyrid-3-yl instead of 2-fluoro-6-chlorophenyl.

Table 79

Table 79 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 79 R¹ is 3,5-dichloropyrid-2-yl instead of 2-fluoro-6-chlorophenyl.

Table 80

Table 80 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 80 R¹ is 4,6-dichloropyrid-3-yl instead of 2-fluoro-6-chlorophenyl.

Table 81

Table 81 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 81 R¹ is 3-trifluoromethylpyrid-4-yl instead of 2-fluoro-6-chlorophenyl.

Table 82

Table 82 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 82 R¹ is 2-trifluoromethylpyrid-3-yl instead of 2-fluoro-6-chlorophenyl.

Table 83

Table 83 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 83 R¹ is 2-fluoro-4-trifluoromethylpyrid-3-yl instead of 2-fluoro-6-chlorophenyl.

Table 84

Table 84 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 84 R¹ is 3-fluoro-5-trifluoromethylpyrid-4-yl instead of 2-fluoro-6-chlorophenyl.

Table 85

Table 85 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 85 R¹ is 4-fluoro-2-trifluoromethylpyrid-3-yl instead of 2-fluoro-6-chlorophenyl.

Table 86

Table 86 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 86 R¹ is 2,6-dichloropyrid-3-yl instead of 2-fluoro-6-chlorophenyl.

Table 87

Table 87 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 87 R¹ is 3,5-dichloropyrid-4-yl instead of 2-fluoro-6-chlorophenyl.

Table 88

Table 88 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 88 R¹ is 3-chloro-6-trifluoromethylpyrid-2-yl instead of 2-fluoro-6-chlorophenyl.

Table 89

Table 89 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 89 R¹ is 3-fluoro-6-trifluoromethylpyrid-2-yl instead of 2-fluoro-6-chlorophenyl.

Table 90

Table 90 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 90 R¹ is pyrid-2-yl instead of 2-fluoro-6-chlorophenyl.

Table 91

Table 91 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 91 R¹ is pyrid-3-yl instead of 2-fluoro-6-chlorophenyl.

Table 92

Table 92 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 92 R¹ is pyrid-4-yl instead of 2-fluoro-6-chlorophenyl.

Table 93

Table 93 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 93 R¹ is 3-fluorothien-2-yl instead of 2-fluoro-6-chlorophenyl.

Table 94

Table 94 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 94 R¹ is 3-chlorothien-2-yl instead of 2-fluoro-6-chlorophenyl.

Table 95

Table 95 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 95 R¹ is 2,4-difluorothien-3-yl instead of 2-fluoro-6-chlorophenyl.

Table 96

Table 96 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 96 R¹ is 2,4-dichlorothien-3-yl instead of 2-fluoro-6-chlorophenyl.

Table 97

Table 97 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table R¹ is 2,4,5-trichlorothien-3-yl instead of 2-fluoro-6-chlorophenyl.

Table 98

Table 98 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 98 R¹ is piperidino instead of 2-fluoro-6-chlorophenyl.

Table 99

Table 99 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 99 R¹ is 2-methylpiperidino instead of 2-fluoro-6-chlorophenyl.

Table 100

Table 100 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 100 R¹ is 2,6-dimethylpiperidino instead of 2-fluoro-6-chlorophenyl.

Table 101

Table 101 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 101 R¹ is morpholino instead of 2-fluoro-6-chlorophenyl.

Table 102

Table 102 consists of 2648 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 102 R¹ is 2,6-dimethylmorpholino instead of 2-fluoro-6-chlorophenyl.

Table 103

Table 103 consists of 201, 248 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 1 to 102 (thus, for example, compound 1 of Table 103 is the same as compound 1 of Table 1, compound 663 of Table 103 is the same as compound 1 of Table 2, compound 19,861 of Table 103 is the same as compound 1 of Table 31, compound 305,844 of Table 103 is the same as compound 3,972 of Table 102) except that in all of the compounds of Table 103 R is F instead of Cl.

Table 104

Table 104 consists of 201,248 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 1 to 102 (thus, for example, compound 1 of Table 104 is the same as compound 1 of Table 1, compound 663 of Table 104 is the same as compound 1 of Table 2, compound 19,861 of Table 104 is the same as compound 1 of Table 31, compound 305,844 of Table 104 is the same as compound 3,972 of Table 102) except that in all of the compounds of Table 104 R is Br instead of Cl.

Table 109

Table 109 consists of 3310 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 1 to 5 (thus, for example, compound 1 of Table 109 is the same as compound 1 of Table 1, compound 663 of Table 109 is the same as compound 1 of Table 2, etc.) except that in all of the compounds of Table 109 X is CF instead of CH.

Table 110

Table 110 consists of 3310c compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 1 to 5 (thus, for example, compound 1 of Table 110 is the same as compound 1 of Table 1, compound 663 of Table 110 is the same as compound 1 of Table 2, etc.) except that in all of the compounds of Table 110 X is CCl instead of CH.

Table 111

Table 111 consists of 3310 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 1 to 5 (thus, for example, compound 1 of Table 111 is the same as compound 1 of Table 1, compound 663 of Table 111 is the same as compound 1 of Table 2, etc.) except that in all of the compounds of Table 111 X is CBr instead of CH.

Table 112

Table 112 consists of 3310 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 1 to 5 (thus, for example, compound 1 of Table 112 is the same as compound 1 of Table 1, compound 663 of Table 112 is the same as compound 1 of Table 2, etc.) except that in all of the compounds of Table 112 X is CCH₃ instead of CH.

Table 113

Table 113 consists of 3310 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 1 to 5 (thus, for example, compound 1 of Table 113 is the same as compound 1 of Table 1, compound 663 of Table 113 is the same as compound 1 of Table 2, etc.) except that in all of the compounds of Table 113 Y is CF instead of CH.

Table 114

Table 114 consists of 3310 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 1 to 5 (thus, for example, compound 1 of Table 114 is the same as compound 1 of Table 1, compound 663 of Table 114 is the same as compound 1 of Table 2, etc.) except that in all of the compounds of Table 114 Y is CCl instead of CH.

Table 115

Table 115 consists of 3310 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 1 to 5 (thus, for example, compound 1 of Table 115 is the same as compound 1 of Table 1, compound 663 of Table 115 is the same as compound 1 of Table 2, etc.) except that in all of the compounds of Table 115 Y is CBr instead of CH.

Table 116

Table 116 consists of 3310 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 1 to 5 (thus, for example, compound 1 of Table 116 is the same as compound 1 of Table 1, compound 663 of Table 116 is the same as compound 1 of Table 2, etc.) except that in all of the compounds of Table 116 Y is CCH₃ instead of CH.

Compounds of formula (7) or (8), which are examples of compounds of general formula (1) where one of R and R² is NR³R⁴, can be made as shown in Scheme 1, in which W, X, Y, Z, R¹, R³ and R⁴ have the meanings given above and R⁷ is C₁₋₄ alkyl.

Compounds of general formula (4) can be prepared from compounds of general formula (2), which are either commercially available or made by methods known in the literature, by reaction with acids of general formula (3), using standard coupling methods, for example by conversion to the acid chloride using a chlorinating agent such as thionyl chloride, followed by reaction of the resultant acid chloride optionally in the presence of a base such as triethylamine, in a suitable solvent such as dichloromethane or toluene. Compounds of general formula (5) can be prepared by treating compounds of general formula (4) with a base such as sodium hydride, optionally in the presence of a Lewis acid such as magnesium oxide, in a suitable solvent such as N,N-dimethylformamide (DMF) or toluene, at between room temperature and 150° C., but preferably at 60-90° C. Compounds of general formula (6) can be prepared by reaction of compounds of general formula (5) with a chlorination reagent such as phosphorus oxychloride, either neat or in a suitable solvent such as toluene, at between 50 and 150° C., but preferably between 80 and 110° C., or in a microwave reactor at between 150 and 300° C., but preferably between 200 and 250° C. Compounds of formula (7) and (8) can be prepared by reaction of compounds of general formula (6) with an amine R³R⁴NH, either neat, or in a suitable solvent such as DMF, between room temperature and 150° C., but preferably between 50 and 80° C. If compounds (7) and (8) are produced as a mixture they can be separated by suitable means such as crystallisation or chromatography under normal or reverse phase conditions.

Compounds of the general formulae (5), (6), (7) and (8) may be derivatised, via the chloro or hydroxy substituents, using routine chemical techniques to form other compounds of the general formula (1). Alternatively, other compounds of the general formula (1) may be prepared using a similar methodology to that described for preparing the compounds (5) to (8) and employing preparative techniques known from the chemical literature.

Compounds of formula (7) can also be made as shown in Scheme 2.

Compounds of general formula (10) can be prepared from compounds of general formula (9), which are either commercially available or made by methods known in the literature, by reaction with acids of general formula (3), using standard coupling methods, for example by conversion to the acid chloride using a chlorinating agent such as thionyl chloride, followed by reaction of the resultant acid chloride optionally in the presence of a base such as triethylamine, in a suitable solvent such as dichloromethane or toluene. Compounds of general formula (11) can be prepared by treating compounds of general formula (10) with a base such as sodium hydride, optionally in the presence of a Lewis acid such as magnesium oxide, in a suitable solvent such as N,N-dimethylformamide (DMF) or toluene, at between room temperature and 150° C., but preferably at 60-90° C. Compounds of general formula (12) can be prepared by reaction of compounds of general formula (11) with a chlorination reagent such as phosphorus oxychloride, either neat or in a suitable solvent such as toluene, at between 50 and 150° C., but preferably between 80 and 110° C., or in a microwave reactor at between 150 and 300° C., but preferably between 200 and 250° C. Compounds of formula (7) can be prepared from compounds of formula (12) by reductive amination, for example by reaction with a ketone or aldehyde in a suitable solvent such as ethanol or toluene, at between room temperature and reflux, optionally in the presence of an acid catalyst such as para-toluenesulphonic acid or a drying agent such as molecular sieves, followed by treatment with a suitable reducing agent such as sodium borohydride, at between −20° C. and 40° C., but preferably at room temperature. The aldehyde or ketone is chosen so that the desired groups R³ and R⁴ are formed after reduction of the product of reaction with the amine (12). For example if compounds of formula (12) are reacted with one equivalent of propionaldehyde and then sodium borohydride, compounds of formula (7) where R³ is npropyl, and R⁴ is hydrogen are formed. If required, the reaction can be repeated with a different aldehyde or ketone. For example, if acetone is used for the second reaction, then compounds of formula (7) where R³ is n-propyl and R⁴ is iso-propyl, are formed. Alternatively compounds of formula (7) can be formed from compounds of formula (12) by alkylation with a group R³LG, by treatment with a suitable base such as sodium hydride in a solvent such as DMF, or a base such as potassium carbonate in a solvent such as acetone or DMF, at between −78° C. and 100° C., but preferably between room temperature and 60° C., followed by treatment with R⁴LG in a second step under the same conditions if required.

Compounds of formula (13) can be prepared as shown in Scheme 3 from compounds of formula (6) by reaction with a source of fluoride ion, such as potassium fluoride, in a suitable solvent such as sulpholane, at a temperature between 50° C. and 200° C., but preferably at 80-150° C. Compounds of formula (14) and/or compounds of formula (15) can be prepared from difluoro compounds of formula (13) by reaction with an amine of formula R³R⁴NH in a suitable solvent such as DMF or CH₂Cl₂, at a temperature of 0° C.-100° C., but preferably at room temperature.

Compounds of general formula (16), where Hal¹ is chlorine or fluorine, can be converted into compounds of formula (17) as shown in Scheme 4. Compounds of general formula (17) where Hal² is bromine or iodine can be formed by reacting compounds of general formula (16) with a metal halide, for example cuprous bromide, in a suitable solvent, for example DMF, at between room temperature and 155° C., but preferably between 70° C. and 155° C.

Further assistance in the preparation of the compounds of formula (1) may be derived from the following publications: Emilio, Toja, et. al., J. Heterocyclic Chem., 23, 1955 (1986), H. Schafer, et. al., J. f. prakt. Chemie, 321(4), 695 (1970) and H. Bredereck et. al., Chem. Ber. 96, 1868-1872 (1993).

The intermediate chemicals having the general formulae (4), (5), (6) and (13):

wherein W, X, Y, Z, R¹ and R⁷ are as define above, other than the compound of formula (6) wherein X and Y are N, W and Z are C—Cl and R¹ is Cl, are believed to be novel compounds and form a further part of this invention.

It should be noted that the intermediate of general formula (5) may exist in the tautomeric forms (a), (b) and (c) as well as in the form shown in formula (5):

The invention as defined by the general formula (5) embraces all such tautomers.

Of particular interest are the intermediates listed in Tables 128 to 132 below. In Table 128 the compounds have the general formula (4) where R⁷ is methyl and W, X, Y, Z and R¹ have the values shown in the table.

TABLE 128 Cmpd No. R¹ W X Y Z 1 2,4,6-trifluorophenyl N CH CH N 2 2,5,6-trifluorophenyl N CH CH N 3 2,3,4,5,6-pentafluorophenyl N CH CH N 4 2,3,5,6-tetrafluorophenyl N CH CH N 5 2,6-difluoro-4-methoxyphenyl N CH CH N 6 2-fluoro-6-chlorophenyl N CH CH N 7 2,6-difluorophenyl N CH CH N 8 2,3,5,6-tetrafluorophenyl N CH CH N 9 2-fluorophenyl N CH CH N 10 2-chlorophenyl N CH CH N 11 2-bromophenyl N CH CH N 12 2,4-dichlorophenyl N CH CH N 13 2,4,6-trifluorophenyl N N CH CH 14 2,5,6-trifluorophenyl N N CH CH 15 2,3,4,5,6-pentafluorophenyl N N CH CH 16 2,3,5,6-tetrafluorophenyl N N CH CH 17 2,6-difluoro-4-methoxyphenyl N N CH CH 18 2-fluoro-6-chlorophenyl N N CH CH 19 2,6-difluorophenyl N N CH CH 20 2,3,5,6-tetrafluorophenyl N N CH CH 21 2-fluorophenyl N N CH CH 22 2-chlorophenyl N N CH CH 23 2-bromophenyl N N CH CH 24 2,4-dichlorophenyl N N CH CH 25 2,4,6-trifluorophenyl CH N N CH 26 2,5,6-trifluorophenyl CH N N CH 27 2,3,4,5,6-pentafluorophenyl CH N N CH 28 2,3,5,6-tetrafluorophenyl CH N N CH 29 2,6-difluoro-4-methoxyphenyl CH N N CH 30 2-fluoro-6-chlorophenyl CH N N CH 31 2,6-difluorophenyl CH N N CH 32 2,3,5,6-tetrafluorophenyl CH N N CH 33 2-fluorophenyl CH N N CH 34 2-chlorophenyl CH N N CH 35 2-bromophenyl CH N N CH 36 2,4-dichlorophenyl CH N N CH 37 2,4,6-trifluorophenyl CH CH N N 38 2,5,6-trifluorophenyl CH CH N N 39 2,3,4,5,6-pentafluorophenyl CH CH N N 40 2,3,5,6-tetrafluorophenyl CH CH N N 41 2,6-difluoro-4-methoxyphenyl CH CH N N 42 2-fluoro-6-chlorophenyl CH CH N N 43 2,6-difluorophenyl CH CH N N 44 2,3,5,6-tetrafluorophenyl CH CH N N 45 2-fluorophenyl CH CH N N 46 2-chlorophenyl CH CH N N 47 2-bromophenyl CH CH N N 48 2,4-dichlorophenyl CH CH N N

Table 129

Table 129 consists of 48 compounds of the general formula (5), where W, X, Y, Z and R¹ have the values given in Table 128. Thus, compound 1 of Table 129 has the same W, X, Y, Z and R¹ values as compound 1 of Table 128, etc.

Table 130

Table 130 consists of 48 compounds of the general formula (6), where W, X, Y, Z and R¹ have the values given in Table 128. Thus, compound 1 of Table 130 has the same W, X, Y, Z and R¹ values as compound 1 of Table 128, etc.

Table 131

Table 131 consists of 48 compounds of the general formula (13), where W, X, Y, Z and R¹ have the values given in Table 128. Thus, compound 1 of Table 131 has the same W, X, Y, Z and R¹ values as compound 1 of Table 128, etc.

Table 132

Table 132 consists of 48 compounds of the general formula (4), where W, X, Y, Z and R¹ have the values given in Table 128 and R⁷ is ethyl. Thus, compound 1 of Table 132 is the same as compound 1 of Table 128 except that in compound 1 of Table 132, K⁷ is ethyl instead of methyl. Similarly, compounds 2 to 48 of Table 132 are the same as compounds 2 to 48 of Table 128 except that in the compounds of Table 132, K⁷ is ethyl.

The compounds of formula (1) are active fungicides and may be used to control one or more of the following pathogens: Pyricularia oryzae (Magnaporthe grisea) on rice and wheat and other Pyricularia spp. on other hosts; Puccinia triticina (or recondita), Puccinia striiformis and other rusts on wheat, Puccinia hordei, Puccinia striiformis and other rusts on barley, and rusts on other hosts (for example turf, rye, coffee, pears, apples, peanuts, sugar beet, vegetables and ornamental plants); Erysiphe cichoracearum on cucurbits (for example melon); Blumeria (or Erysiphe) graminis (powdery mildew) on barley, wheat, rye and turf and other powdery mildews on various hosts, such as Sphaerotheca macularis on hops, Sphaerotheca fusca (Sphaerotheca fuliginea) on cucurbits (for example cucumber), Leveillula taurica on tomatoes, aubergine and green pepper, Podosphaera leucotricha on apples and Uncinula necator on vines; Cochliobolus spp., Helminthosporium spp., Drechslera spp. (Pyrenophora spp.), Rhynchosporium spp., Mycosphaerella graminicola (Septoria tritici) and Phaeosphaeria nodorum (Stagonospora nodorum or Septoria nodorum), Pseudocercosporella herpotrichoides and Gaeumannomyces graminis on cereals (for example wheat, barley, rye), turf and other hosts; Cercospora arachidicola and Cercosporidium personatum on peanuts and other Cercospora spp. on other hosts, for example sugar beet, bananas, soya beans and rice; Botrytis cinerea (grey mould) on tomatoes, strawberries, vegetables, vines and other hosts and other Botrytis spp. on other hosts; Alternaria spp. on vegetables (for example carrots), oil-seed rape, apples, tomatoes, potatoes, cereals (for example wheat) and other hosts; Venturia spp. (including Venturia inaequalis (scab)) on apples, pears, stone fruit, tree nuts and other hosts; Cladosporium spp. on a range of hosts including cereals (for example wheat) and tomatoes; Monilinia spp. on stone fruit, tree nuts and other hosts; Didymella spp. on tomatoes, turf, wheat, cucurbits and other hosts; Phoma spp. on oil-seed rape, turf, rice, potatoes, wheat and other hosts; Aspergillus spp. and Aureobasidium spp. on wheat, lumber and other hosts; Ascochyta spp. on peas, wheat, barley and other hosts; Stemphylium spp. (Pleospora spp.) on apples, pears, onions and other hosts; summer diseases (for example bitter rot (Glomerella cingulata), black rot or frogeye leaf spot (Botryosphaeria obtusa), Brooks fruit spot (Mycosphaerella pomi), Cedar apple rust (Gymnosporangium juniperi-virginianae), sooty blotch (Gloeodes pomigena), flyspeck (Schizothyrium pomi) and white rot (Botryosphaeria dothidea)) on apples and pears; Plasmopara viticola on vines; other downy mildews, such as Bremia lactucae on lettuce, Peronospora spp. on soybeans, tobacco, onions and other hosts, Pseudoperonospora humuli on hops and Pseudoperonospora cubensis on cucurbits; Pythium spp. (including Pythium ultimum) on turf and other hosts; Phytophthora infestans on potatoes and tomatoes and other Phytophthora spp. on vegetables, strawberries, avocado, pepper, ornamentals, tobacco, cocoa and other hosts; Thanatephorus cucumeris on rice and turf and other Rhizoctonia spp. on various hosts such as wheat and barley, peanuts, vegetables, cotton and turf, Sclerotinia spp. on turf, peanuts, potatoes, oil-seed rape and other hosts; Sclerotium spp. on turf, peanuts and other hosts; Gibberella fujikuroi on rice; Colletotrichum spp. on a range of hosts including turf, coffee and vegetables; Laetisaria fuciformis on turf, Mycosphaerella spp. on bananas, peanuts, citrus, pecans, papaya and other hosts; Diaporthe spp. on citrus, soybean, melon, pears, lupin and other hosts; Elsinoe spp. on citrus, vines, olives, pecans, roses and other hosts; Verticillium spp. on a range of hosts including hops, potatoes and tomatoes; Pyrenopeziza spp. on oil-seed rape and other hosts; Oncobasidium theobromae on cocoa causing vascular streak dieback; Fusarium spp., Typhula spp., Microdochium nivale, Ustilago spp., Urocystis spp., Tilletia spp. and Claviceps purpurea on a variety of hosts but particularly wheat, barley, turf and maize; Ramularia spp. on sugar beet, barley and other hosts; post-harvest diseases particularly of fruit (for example Penicillium digitatum, Penicillium italicum and Trichoderma viride on oranges, Colletotrichum musae and Gloeosporium musarum on bananas and Botrytis cinerea on grapes); other pathogens on vines, notably Eutypa lata, Guignardia bidwellii, Phellinus igniarus, Phomopsis viticola, Pseudopeziza tracheiphila and Stereum hirsutum; other pathogens on trees (for example Lophodermium seditiosum) or lumber, notably Cephaloascus fragrans, Ceratocystis spp., Ophiostomapiceae, Penicillium spp., Trichoderma pseudokoningii, Trichoderma viride, Trichoderma harzianum, Aspergillus niger, Leptographium lindbergi and Aureobasidium pullulans; and fungal vectors of viral diseases (for example Polymyxa graminis on cereals as the vector of barley yellow mosaic virus (BYMV) and Polymyxa betae on sugar beet as the vector of rhizomania).

A compound of formula (1) may move acropetally, basipetally or locally in plant tissue to be active against one or more fungi. Moreover, a compound of formula (1) may be volatile enough to be active in the vapour phase against one or more fungi on the plant.

The invention therefore provides a method of combating or controlling phytopatho-genic fungi which comprises applying a fungicidally effective amount of a compound of formula (1), or a composition containing a compound of formula (1), to a plant, to a seed of a plant, to the locus of the plant or seed or to soil or any other plant growth medium, e.g. nutrient solution.

The term “plant” as used herein includes seedlings, bushes and trees. Furthermore, the fungicidal method of the invention includes protectant, curative, systemic, eradicant and antisporulant treatments.

The compounds of formula (1) are preferably used for agricultural, horticultural and turfgrass purposes in the form of a composition.

In order to apply a compound of formula (1) to a plant, to a seed of a plant, to the locus of the plant or seed or to soil or any other growth medium, a compound of formula (1) is usually formulated into a composition which includes, in addition to the compound of formula (1), a suitable inert diluent or carrier and, optionally, a surface active agent (SFA). SFAs are chemicals that are able to modify the properties of an interface (for example, liquid/solid, liquid/air or liquid/liquid interfaces) by lowering the interfacial tension and thereby leading to changes in other properties (for example dispersion, emulsification and wetting). It is preferred that all compositions (both solid and liquid formulations) comprise, by weight, 0.0001 to 95%, more preferably 1 to 85%, for example 5 to 60%, of a compound of formula (1). The composition is generally used for the control of fungi such that a compound of formula (1) is applied at a rate of from 0.1 g to 10 kg per hectare, preferably from 1 g to 6 kg per hectare, more preferably from 1 g to 1 kg per hectare.

When used in a seed dressing, a compound of formula (1) is used at a rate of 0.0001 g to 10 g (for example 0.001 g or 0.05 g), preferably 0.005 g to 10 g, more preferably 0.005 g to 4 g, per kilogram of seed.

In another aspect the present invention provides a fungicidal composition comprising a fungicidally effective amount of a compound of formula (1) and a suitable carrier or diluent therefor.

In a still further aspect the invention provides a method of combating and controlling fungi at a locus, which comprises treating the fungi, or the locus of the fungi with a fungicidally effective amount of a composition comprising a compound of formula (1).

The compositions can be chosen from a number of formulation types, including dustable powders (DP), soluble powders (SP), water soluble granules (SG), water dispersible granules (WG), wettable powders (WP), granules (GR) (slow or fast release), soluble concentrates (SL), oil miscible liquids (OL), ultra low volume liquids (UL), emulsifiable concentrates (EC), dispersible concentrates (DC), emulsions (both oil in water (EW) and water in oil (EO)), micro-emulsions (ME), suspension concentrates (SC), aerosols, fogging/smoke formulations, capsule suspensions (CS) and seed treatment formulations. The formulation type chosen in any instance will depend upon the particular purpose envisaged and the physical, chemical and biological properties of the compound of formula (1).

Dustable powders (DP) may be prepared by mixing a compound of formula (1) with one or more solid diluents (for example natural clays, kaolin, pyrophillite, bentonite, alumina, montmorillonite, kieselguhr, chalk, diatomaceous earths, calcium phosphates, calcium and magnesium carbonates, sulphur, lime, flours, talc and other organic and inorganic solid carriers) and mechanically grinding the mixture to a fine powder.

Soluble powders (SP) may be prepared by mixing a compound of formula (1) with one or more water-soluble inorganic salts (such as sodium bicarbonate, sodium carbonate or magnesium sulphate) or one or more water-soluble organic solids (such as a polysaccharide) and, optionally, one or more wetting agents, one or more dispersing agents or a mixture of said agents to improve water dispersibility/solubility. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water soluble granules (SG).

Wettable powders (WP) may be prepared by mixing a compound of formula (1) with one or more solid diluents or carriers, one or more wetting agents and, preferably, one or more dispersing agents and, optionally, one or more suspending agents to facilitate the dispersion in liquids. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water dispersible granules (WG).

Granules (GR) may be formed either by granulating a mixture of a compound of formula (1) and one or more powdered solid diluents or carriers, or from pre-formed blank granules by absorbing a compound of formula (1) (or a solution thereof, in a suitable agent) in a porous granular material (such as pumice, attapulgite clays, fuller's earth, kieselguhr, diatomaceous earths or ground corn cobs) or by adsorbing a compound of formula (1) (or a solution thereof, in a suitable agent) on to a hard core material (such as sands, silicates, mineral carbonates, sulphates or phosphates) and drying if necessary. Agents which are commonly used to aid absorption or adsorption include solvents (such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones and esters) and sticking agents (such as polyvinyl acetates, polyvinyl alcohols, dextrins, sugars and vegetable oils). One or more other additives may also be included in granules (for example an emulsifying agent, wetting agent or dispersing agent).

Dispersible Concentrates (DC) may be prepared by dissolving a compound of formula (1) in water or an organic solvent, such as a ketone, alcohol or glycol ether. These solutions may contain a surface active agent (for example to improve water dilution or prevent crystallisation in a spray tank).

Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) may be prepared by dissolving a compound of formula (1) in an organic solvent (optionally containing one or more wetting agents, one or more emulsifying agents or a mixture of said agents). Suitable organic solvents for use in ECs include aromatic hydrocarbons (such as alkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100, SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark), ketones (such as cyclohexanone or methylcyclohexanone), alcohols (such as benzyl alcohol, furfuryl alcohol or butanol), N-alkypyrrolidones (such as N-methylpyrrolidone or N-octylpyrrolidone), dimethyl amides of fatty acids (such as C₈-C₁₀ fatty acid dimethylamide) and chlorinated hydrocarbons. An EC product may spontaneously emulsify on addition to water, to produce an emulsion with sufficient stability to allow spray application through appropriate equipment. Preparation of an EW involves obtaining a compound of formula (1) either as a liquid (if it is not a liquid at room temperature, it may be melted at a reasonable temperature, typically below 70° C.) or in solution (by dissolving it in an appropriate solvent) and then emulsifying the resultant liquid or solution into water containing one or more SFAs, under high shear, to produce an emulsion. Suitable solvents for use in EWs include vegetable oils, chlorinated hydrocarbons (such as chlorobenzenes), aromatic solvents (such as alkylbenzenes or alkylnaphthalenes) and other appropriate organic solvents that have a low solubility in water.

Microemulsions (ME) may be prepared by mixing water with a blend of one or more solvents with one or more SFAs, to produce spontaneously a thermodynamically stable isotropic liquid formulation. A compound of formula (1) is present initially in either the water or the solvent/SFA blend. Suitable solvents for use in MEs include those hereinbefore described for use in ECs or in EWs. An ME may be either an oil-in-water or a water-in-oil system (which system is present may be determined by conductivity measurements) and may be suitable for mixing water-soluble and oil-soluble pesticides in the same formulation. An ME is suitable for dilution into water, either remaining as a microemulsion or forming a conventional oil-in-water emulsion.

Suspension concentrates (SC) may comprise aqueous or non-aqueous suspensions of finely divided insoluble solid particles of a compound of formula (1). SCs may be prepared by ball or bead milling the solid compound of formula (1) in a suitable medium, optionally with one or more dispersing agents, to produce a fine particle suspension of the compound. One or more wetting agents may be included in the composition and a suspending agent may be included to reduce the rate at which the particles settle. Alternatively, a compound of formula (1) may be dry milled and added to water, containing agents hereinbefore described, to produce the desired end product.

Aerosol formulations comprise a compound of formula (1) and a suitable propellant (for example n-butane). A compound of formula (1) may also be dissolved or dispersed in a suitable medium (for example water or a water miscible liquid, such as n-propanol) to provide compositions for use in non-pressurised, hand-actuated spray pumps.

A compound of formula (1) may be mixed in the dry state with a pyrotechnic mixture to form a composition suitable for generating, in an enclosed space, a smoke containing the compound.

Capsule suspensions (CS) may be prepared in a manner similar to the preparation of EW formulations but with an additional polymerisation stage such that an aqueous dispersion of oil droplets is obtained, in which each oil droplet is encapsulated by a polymeric shell and contains a compound of formula (1) and, optionally, a carrier or diluent therefor. The polymeric shell may be produced by either an interfacial polycondensation reaction or by a coacervation procedure. The compositions may provide for controlled release of the compound of formula (1) and they may be used for seed treatment. A compound of formula (1) may also be formulated in a biodegradable polymeric matrix to provide a slow, controlled release of the compound.

A composition may include one or more additives to improve the biological performance of the composition (for example by improving wetting, retention or distribution on surfaces; resistance to rain on treated surfaces; or uptake or mobility of a compound of formula (1)). Such additives include surface active agents, spray additives based on oils, for example certain mineral oils or natural plant oils (such as soy bean and rape seed oil), and blends of these with other bio-enhancing adjuvants (ingredients which may aid or modify the action of a compound of formula (1)).

A compound of formula (1) may also be formulated for use as a seed treatment, for example as a powder composition, including a powder for dry seed treatment (DS), a water soluble powder (SS) or a water dispersible powder for slurry treatment (WS), or as a liquid composition, including a flowable concentrate (FS), a solution (LS) or a capsule suspension (CS). The preparations of DS, SS, WS, FS and LS compositions are very similar to those of, respectively, DP, SP, WP, SC and DC compositions described above. Compositions for treating seed may include an agent for assisting the adhesion of the composition to the seed (for example a mineral oil or a film-forming barrier).

Wetting agents, dispersing agents and emulsifying agents may be SFAs of the cationic, anionic, amphoteric or non-ionic type.

Suitable SFAs of the cationic type include quaternary ammonium compounds (for example cetyltrimethyl ammonium bromide), imidazolines and amine salts.

Suitable anionic SFAs include alkali metals salts of fatty acids, salts of aliphatic monoesters of sulphuric acid (for example sodium lauryl sulphate), salts of sulphonated aromatic compounds (for example sodium dodecylbenzenesulphonate, calcium dodecyl-benzenesulphonate, butylnaphthalene sulphonate and mixtures of sodium di-isopropyl- and tri-isopropyl-naphthalene sulphonates), ether sulphates, alcohol ether sulphates (for example sodium laureth-3-sulphate), ether carboxylates (for example sodium laureth-3-carboxylate), phosphate esters (products from the reaction between one or more fatty alcohols and phosphoric acid (predominately mono-esters) or phosphorus pentoxide (predominately di-esters), for example the reaction between lauryl alcohol and tetraphosphoric acid; additionally these products may be ethoxylated), sulphosuccinamates, paraffin or olefine sulphonates, taurates and lignosulphonates.

Suitable SFAs of the amphoteric type include betaines, propionates and glycinates.

Suitable SFAs of the non-ionic type include condensation products of alkylene oxides, such as ethylene oxide, propylene oxide, butylene oxide or mixtures thereof, with fatty alcohols (such as oleyl alcohol or cetyl alcohol) or with alkylphenols (such as octylphenol, nonylphenol or octylcresol); partial esters derived from long chain fatty acids or hexitol anhydrides; condensation products of said partial esters with ethylene oxide; block polymers (comprising ethylene oxide and propylene oxide); alkanolamides; simple esters (for example fatty acid polyethylene glycol esters); amine oxides (for example lauryl dimethyl amine oxide); and lecithins.

Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose) and swelling clays (such as bentonite or attapulgite).

A compound of formula (1) may be applied by any of the known means of applying fungicidal compounds. For example, it may be applied, formulated or unformulated, to any part of the plant, including the foliage, stems, branches or roots, to the seed before it is planted or to other media in which plants are growing or are to be planted (such as soil surrounding the roots, the soil generally, paddy water or hydroponic culture systems), directly or it may be sprayed on, dusted on, applied by dipping, applied as a cream or paste formulation, applied as a vapour or applied through distribution or incorporation of a composition (such as a granular composition or a composition packed in a water-soluble bag) in soil or an aqueous environment.

A compound of formula (1) may also be injected into plants or sprayed onto vegetation using electrodynamic spraying techniques or other low volume methods, or applied by land or aerial irrigation systems.

Compositions for use as aqueous preparations (aqueous solutions or dispersions) are generally supplied in the form of a concentrate containing a high proportion of the active ingredient, the concentrate being added to water before use. These concentrates, which may include DCs, SCs, ECs, EWs, MEs SGs, SPs, WPs, WGs and CSs, are often required to withstand storage for prolonged periods and, after such storage, to be capable of addition to water to form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment. Such aqueous preparations may contain varying amounts of a compound of formula (1) (for example 0.0001 to 10%, by weight) depending upon the purpose for which they are to be used.

A compound of formula (1) may be used in mixtures with fertilisers (for example nitrogen-, potassium- or phosphorus-containing fertilisers). Suitable formulation types include granules of fertiliser. The mixtures suitably contain up to 25% by weight of the compound of formula (1).

The invention therefore also provides a fertiliser composition comprising a fertiliser and a compound of formula (1).

The compositions of this invention may contain other compounds having biological activity, for example micronutrients or compounds having similar or complementary fungicidal activity or which possess plant growth regulating, herbicidal, insecticidal, nematicidal or acaricidal activity.

By including another fungicide, the resulting composition may have a broader spectrum of activity or a greater level of intrinsic activity than the compound of formula (1) alone. Further the other fungicide may have a synergistic effect on the fungicidal activity of the compound of formula (1).

The compound of formula (1) may be the sole active ingredient of the composition or it may be admixed with one or more additional active ingredients such as a pesticide, fungicide, synergist, herbicide or plant growth regulator where appropriate. An additional active ingredient may: provide a composition having a broader spectrum of activity or increased persistence at a locus; synergise the activity or complement the activity (for example by increasing the speed of effect or overcoming repellency) of the compound of formula (1); or help to overcome or prevent the development of resistance to individual components. The particular additional active ingredient will depend upon the intended utility of the composition.

Examples of fungicidal compounds which may be included in the composition of the invention are AC 382042 (N-(1-cyano-1,2-dimethylpropyl)-2-(2,4-dichlorophenoxy) propionamide), acibenzolar-S-methyl, alanycarb, aldimorph, anilazine, azaconazole, azafenidin, azoxystrobin, benalaxyl, benomyl, benthiavalicarb, biloxazol, bitertanol, blasticidin S, boscalid (new name for nicobifen), bromuconazole, bupirimate, captafol, captan, carbendazim, carbendazim chlorhydrate, carboxin, carpropamid, carvone, CGA 41396, CGA 41397, chinomethionate, chlorbenzthiazone, chlorothalonil, chlorozolinate, clozylacon, copper containing compounds such as copper oxychloride, copper oxyquinolate, copper sulphate, copper tallate, and Bordeaux mixture, cyamidazosulfamid, cyazofamid (IKF-916), cyflufenamid, cymoxanil, cyproconazole, cyprodinil, debacarb, di-2-pyridyl disulphide 1,1′-dioxide, dichlofluanid, diclocymet, diclomezine, dicloran, diethofencarb, difenoconazole, difenzoquat, diflumetorim, O,O-di-iso-propyl-S-benzyl thiophosphate, dimefluazole, dimetconazole, dimethirimol, dimethomorph, dimoxystrobin, diniconazole, dinocap, dithianon, dodecyl dimethyl ammonium chloride, dodemorph, dodine, doguadine, edifenphos, epoxiconazole, ethaboxam, ethirimol, ethyl (Z)-N-benzyl-N([methyl(methyl-thioethylideneaminooxycarbonyl)amino]thio)-β-alaninate, etridiazole, famoxadone, fenamidone, fenarimol, fenbuconazole, fenfuram, fenhexamid, fenoxanil (AC 382042), fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, flumetover, flumorph, fluoroimide, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutolanil, flutriafol, folpet, fosetyl-aluminium, fuberidazole, furalaxyl, furametpyr, guazatine, hexaconazole, hydroxyisoxazole, hymexazole, imazalil, imibenconazole, iminoctadine, iminoctadine triacetate, ipconazole, iprobenfos, iprodione, iprovalicarb, isopropanyl butyl carbamate, isoprothiolane, kasugamycin, kresoxim-methyl, LY186054, LY211795, LY 248908, mancozeb, maneb, mefenoxam, mepanipyrim, mepronil, metalaxyl, metalaxyl M, metconazole, metiram, metiram-zinc, metominostrobin, metrafenone, MON65500 (N-allyl-4,5-dimethyl-2-trimethylsilylthiophene-3-carboxamide), myclobutanil, NTN0301, neoasozin, nickel dimethyldithiocarbamate, nitrothale-isopropyl, nuarimol, ofurace, organomercury compounds, orysastrobin, oxadixyl, oxasulfuron, oxolinic acid, oxpoconazole, oxycarboxin, pefurazoate, penconazole, pencycuron, phenazin oxide, phosphorus acids, phthalide, picoxystrobin, polyoxin D, polyram, probenazole, prochloraz, procymidone, propamocarb, propamocarb hydrochloride, propiconazole, propineb, propionic acid, proquinazid, prothioconazole, pyraclostrobin, pyrazophos, pyrifenox, pyrimethanil, pyroquilon, pyroxyfur, pyrrolnitrin, quaternary ammonium compounds, quinomethionate, quinoxyfen, quintozene, silthiofam (MON 65500), S-imazalil, simeconazole, sipconazole, sodium pentachlorophenate, spiroxamine, streptomycin, sulphur, tebuconazole, tecloftalam, tecnazene, tetraconazole, thiabendazole, thifluzamide, 2-(thiocyanomethylthio)-benzothiazole, thiophanate-methyl, thiram, tiadinil, timibenconazole, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triazbutil, triazoxide, tricyclazole, tridemorph, trifloxystrobin, triflumizole, triforine, triticonazole, validamycin A, vapam, vinclozolin, XRD-563, zineb, ziram, zoxamide and compounds of the formulae:

The compounds of formula (1) may be mixed with soil, peat or other rooting media for the protection of plants against seed-borne, soil-borne or foliar fungal diseases.

Some mixtures may comprise active ingredients, which have significantly different physical, chemical or biological properties such that they do not easily lend themselves to the same conventional formulation type. In these circumstances other formulation types may be prepared. For example, where one active ingredient is a water insoluble solid and the other a water insoluble liquid, it may nevertheless be possible to disperse each active ingredient in the same continuous aqueous phase by dispersing the solid active ingredient as a suspension (using a preparation analogous to that of an SC) but dispersing the liquid active ingredient as an emulsion (using a preparation analogous to that of an EW). The resultant composition is a suspoemulsion (SE) formulation.

The invention is illustrated by the following Examples in which the following abbreviations are used:

ml=millilitres f=fine g=grammes THF=tetrahydrofuran ppm=parts per million DCM=dichloromethane s=singlet DMF═N,N-dimethylformamide d=doublet DMSO=dimethylsulphoxide t=triplet DMAP=4-dimethylaminopyridine q=quartet NMR=nuclear magnetic resonance m=multiplet HPLC=high performance liquid b=broad chromatography

EXAMPLE 1

This Example illustrates the preparation of [6-chloro-7-(2,4,6-trifluorophenyl)-pyrido[2,3-b]pyrazin-8-yl]-isopropylamine (Compound No. 3, Table 1).

Step 1 Methyl 2-amino-3-pyrazine carboxylate (2.2 g) was dissolved in dry DCM (20 ml) to give a cloudy pale yellow solution, and pyridine (2 ml) in dry DCM (12 ml) was added. The stirred suspension was cooled in an ice bath, and 2,4,6-trifluorophenylacetyl chloride (3.0 g) in dry DCM (13 ml) was added dropwise. The reaction gradually became a deep orange, and then went clear. It was stirred for 6 hours and stood overnight. The reaction mixture was washed with water, brine, and then dilute hydrochloric acid, and the DCM layer was dried over magnesium sulphate. The solvent was evaporated to yield an orange solid which was triturated with ether, to give methyl 2-[2,4,6-trifluorophenylacetylamino]-3-pyrazine carboxylate as a yellow solid (1.5 g).

¹H NMR (CDCl₃) δ ppm: 4.03 (s, 5H), 6.74 (t, 2H), 8.43 (d, 1H), 8.61 (d, 1H) 10.9 (s, 1H).

Step 2

The product of Step 1 (3.25 g) was dissolved in DMF (10 ml) and added dropwise to a stirred suspension of sodium hydride (0.60 g of an 80% dispersion in mineral oil) in DMF (80 ml). There was an immediate reaction, and the mixture was stirred at room temperature for 2 hours, and at 80° C. for 8 hours. The reaction mixture was cooled and evaporated to give a yellow solid (3 g), which was then acidified with dilute hydrochloric acid. The resultant white suspension was filtered and collected, washed with ether and dried to give 6,8-dihydroxy-7-(2,4,6-trifluorophenyl)pyrido[2,3-b]pyrazine (1.8 g).

¹H NMR (d⁶-DMSO) δ ppm: 7.25 (t, 2H), 8.6 (fd, 1H), 8.7 (fd, 1H), 12.6 (s, 1H).

Step 3

The product from Step 2 (0.90 g) was added portion-wise to phosphorus oxychloride (10 ml) with stirring. The reaction was exothermic. The mixture became brown with a fine suspension, and was then refluxed for 6 hours. Excess phosphorus oxychloride was evaporated, the mixture was diluted with DCM, and then washed with water to give a black oil, which was purified by flash column chromatography on silica gel (40-60) eluting with diethyl ether, to give 6,8-dichloro-7-(2,4,6-trifluorophenyl)pyrido[2,3-b]pyrazine as a dark oil (0.40 g).

¹H NMR (CDCl₃) δ ppm: 6.9 (t, 2H), 9.1 (d, 1H), 9.2 (d, 1H).

Alternative Procedure for Step 3

Phosphorus oxychloride (20.90 g) was added over 15 minutes to a suspension of the product from Step 2 (10.0 g), in 1,2-dichloroethane (80 ml) containing DMF (5.0 g) maintained at a temperature between 79°-81° C. Stirring was continued at this temperature for 3 hours, and the reaction was then cooled. The mixture was poured carefully into saturated sodium bicarbonate solution (500 ml) keeping the temperature below 30° C. After stirring for 20 minutes the product was extracted with ethyl acetate, washed with water and brine and dried over sodium sulphate. The solvent was evaporated to yield a dark red oil, which was purified by flash chromatography eluting with cyclohexane:ethyl acetate, 4:1 to give 6,8-dichloro-7-(2,4,6-trifluorophenyl)pyrido[2,3-b]pyrazine as a light brown solid (7.5 g), m.p. 139-141° C.

Step 4

The product from Step 3 (0.20 g), isopropylamine (1.0 ml) and N-ethyl-diisopropylamine (0.20 g) were refluxed in a sealed tube at 90° C. for 17 hours. The dark coloured reaction mixture was evaporated to give an oil, which was purified by flash column chromatography on silica gel (40-60) in diethyl ether.

A fraction containing a mixture of isomers (0.080 g), was obtained, and a portion of this mixture (0.020 g) was purified by reverse phase HPLC on a Kromasil 100-5C18 column, eluting with methanol:water (65:35) to give [6-chloro-7-(2,4,6-trifluorophenyl)-pyrido[2,3-b]pyrazin-8-yl]-isopropylamine as a frothy solid (0.013 g).

¹H NMR (CDCl₃) δ ppm: 1.1 (d, 6H), 3.26 (m, 1H), 6.84 (m, 2H), 6.95 (bd, 1H), 8.67 (d, 1H), 9.0 (d, 1H).

EXAMPLE 2

This Example illustrates the preparation of [6-fluoro-7-(2,4,6-trifluorophenyl)-pyrido[2,3-b]pyrazin-8-yl]-isopropylamine (Compound No. 3, Table 103)

Step 1

6,8-Dichloro-7-(2,4,6-trifluorophenyl)-pyrido[2,3-b]pyrazine (1.25 g) and potassium fluoride (0.66 g, spray dried) in dry sulpholane (5 ml) were heated to 130° C. for 16 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with water and brine and dried over sodium sulphate. After evaporation of the solvent, the remaining oil was purified by flash chromatography on silica gel eluting with cyclohexane:ethyl acetate, 3:1 to yield 6,8-difluoro-7-(2,4,6-trifluorophenyl)-pyrido[2,3-b]-pyrazine as a slightly brownish solid (0.79 g), m.p. 120-121° C.

Step 2

The product from Step 1 (0.30 g) was added to a suspension of isopropylamine (0.090 g), potassium carbonate (0.21 g) and a catalytic amount of DMAP in DMF (3 ml), and the mixture was stirred at room temperature for 19 hours. After addition of ethyl acetate, the mixture was washed with water and brine, dried over sodium sulphate, filtered and the solvent evaporated. The residue was purified by flash chromatography eluting with toluene:ethyl acetate, 9:1 to give [6-fluoro-7-(2,4,6-trifluorophenyl)-pyrido[2,3-b]pyrazin-8-yl]-isopropylamine as a yellow powder (0.20 g), m.p. 127-128° C.

EXAMPLE 3

This Example illustrates the preparation of [6-chloro-7-(2,4,6-trifluorophenyl)-pyrido[3,2-c]pyridazin-8-yl]-isopropylamine (Compound No. 3, Table 11).

Step 1

A solution of 4-aminopyridazine-3-carbonitrile (0.248 g, prepared as in J. Het. Chem. (1970), 3, 467-473) in absolute ethanol (30 ml) was saturated with hydrogen chloride gas, the flask being cooled in an ice bath. The ice bath was then removed and the resulting solution was refluxed for 18 hours. It was then cooled, the solvent evaporated, and cold, saturated aqueous sodium bicarbonate was added. The aqueous phase was then extracted with DCM, the organic phases were combined, dried over magnesium sulphate, filtered and evaporated to give 4-aminopyridazine-3-carboxylic acid ethyl ester as a white solid (0.229 g). The aqueous phase was evaporated, DCM was added, the organic phase was isolated, dried over magnesium sulphate, filtered and evaporated under vacuo to give further ester as a white solid (0.010 g), m.p. 149-150° C.

¹H NMR (CDCl₃) δ ppm: 1.48 (t, 3H), 4.52 (q, 2H), 6.73 (d, 1H), 8.75 (d, 1H).

Step 2

A mixture of the product from Step 1 (0.239 g) and DMAP (0.175 g) in dry toluene (1 ml) was added to 2,4,6-trifluorophenylacetyl chloride (crude product from reaction of 0.275 g 2,4,6-trifluorophenylacetic acid and oxalyl chloride) and a few drops of DMF in toluene (1 ml) at room temperature, giving a thick yellow precipitate. The stirred suspension was heated for 3 hours at reflux, becoming dark brown/green with a green precipitate. It was left to stand overnight for 18 hours. The solid was collected and washed with diethyl ether. The dark green filtrate was evaporated to give a dark green liquid which was purified by flash column chromatography on silica gel (40-60) eluting with ethyl acetate to give 4-[2-(2,4,6-trifluorophenyl)-acetylamino]-pyridazine-3-carboxylic acid ethyl ester as green/yellow oil that solidified on standing (0.307 g).

¹H NMR (CDCl₃) δ ppm: 1.50 (t, 3H), 3.87 (s, 2H), 4.55 (q, 2H), 6.77 (t, 2H), 8.78 (d, 1H), 9.15 (d, 1H), 11.20 (bs, 1H).

Step 3

The product from Step 2 (0.307 g) and potassium carbonate (0.25 g) were stirred in dry DMF (10 ml) at 110° C. for 2 hours and then cooled and stood for 18 hours. The DMF was evaporated and the resulting brown solid was triturated with diethyl ether and the organic phase decanted. The solid was dissolved in water then acidified with dilute hydrochloric acid to neutrality. Most of the aqueous phase was then evaporated, leading to precipitation of a black solid that was filtered, and the yellow/brown aqueous phase was evaporated to dryness, affording a residue that was dissolved in methanol, the insoluble inorganic salts were filtered and the organic phase was evaporated to dryness to give 7-(2,4,6-trifluorophenyl)-5H-pyrido[3,2-c]pyridazine-6,8-dione as a light brown/beige solid (0.258 g).

¹H NMR (CD₃OD) δ ppm: 6.83 (2d, 2H), 7.44 (d, 1H), 9.00 (d, 1H).

Step 4

Phosphorus oxychloride (0.048 ml) was added to the product from Step 3 (0.05 g) in 1,2-dichloroethane (2 ml) containing a catalytic amount of DMF. The suspension was stirred and refluxed for 1 hour and then stood for 18 hours, and then refluxed for a further hour and then allowed to cool. The excess phosphorus oxychloride was evaporated to give a brown oil, which was dissolved in DCM and washed with cold water. The organic layer was separated and dried over magnesium sulphate, filtered and evaporated to give a brown oil, which was purified by flash column chromatography on silica gel (40-60) eluting with diethyl ether to give 6,8-dichloro-7-(2,4,6-trifluorophenyl)-pyrido[3,2-c]pyridazine as a yellow oil (0.015 g).

¹H NMR (CDCl₃) δ ppm: 6.92 (m, 2H), 8.11 (d, 1H), 9.71 (d, 1H).

Step 5

Isopropylamine (0.5 ml) was added to the product from Step 4 (0.015 g) dissolved in DCM (1 ml) containing dimethylacetamide (0.3 ml) in a sealed tube. The yellow solution became yellow/greenish. The vessel was then sealed and stirred at room temperature. The solvents were evaporated and the crude residue was purified using preparative thin layer chromatography silica gel plates eluting with ethyl acetate:hexane 1:1 to give [6-Chloro-7-(2,4,6-trifluorophenyl)-pyrido[3,2-c]pyridazin-8-yl]-isopropylamine (0.003 g).

¹H NMR (CDCl₃) δ ppm: 1.16 (d, 6H), 3.41 (m, 1H), 6.85 (dd, 2H), 7.79 (bs, 1H), 7.84 (d, 1H). 9.40 (d, 1H).

EXAMPLE 4

This Example illustrates the preparation of [2-chloro-3-(2,4,6-trifluorophenyl)-pyrido[2,3-d]pyridazin-4-yl]-isopropylamine (Compound No. 3, Table 21).

Step 1

5-Aminopyridazine-4-carboxylic acid ethyl ester (1.26 g, prepared according to J. Het. Chem., (1968), 5, 845) was dissolved in dry toluene (125 ml) at 90° C., and DMAP (0.92 g) was added. 2,4,6-Trifluorophenylacetyl chloride (1.75 g of 95% purity material) was added dropwise with stirring at 70° C., and a white solid precipitated. The reaction was stirred at reflux for 5 hours and then filtered hot. The filtrate was evaporated to give 5-[2-(2,4,6-trifluorophenyl)-acetylamino]-pyridazine-4-carboxylic acid ethyl ester as a white solid (2.6 g), m.p. 143-144° C.

¹H NMR (CDCl₃) δ ppm: 1.45 (t, 3H), 3.90 (s, 2H), (4.45 (q, 2H), 6.75 (m, 2H), 9.45 (s1H), 10.60 (s, 1H), 11.1 (bs, 1H).

Step 2

The product from Step 1 (2.5 g) was dissolved in dry THF (50 ml) and the flask purged with nitrogen. Sodium bis-trimethylsilylamide (22.1 ml of a 1M solution in THF) was added dropwise with stirring at 0° C. A yellow precipitate appeared, and the reaction was stirred for 3 hours at 0° C. The reaction was quenched with concentrated hydrochloric acid (5 ml) at 0° C. and then poured onto ice water, extracted with DCM and dried over magnesium sulphate. The solvent was evaporated to give 3-(2,4,6-trifluorophenyl)-1H-pyrido[2,3-d]pyridazine-2,4-dione as a yellow solid. Further product crystallised out of the aqueous solution overnight, to give a total yield of 1.29 g, m.p. >300° C.

¹H NMR (d⁶-DMSO) δ ppm: 7.25 (m, 2H), 9.17 (s, 1H), 9.47 (s, 1H), 12.30 (bs, 1H).

Step 3

The product from Step 2 (0.10 g) was heated to 90° C. with phosphorus oxychloride (1.6 ml) with stirring. After 1 hour a clear yellow solution was obtained and the excess solvent was evaporated and ice water was added, giving a yellow solid. This was extracted with DCM, and the solution dried over magnesium sulphate and evaporated to give 2,4-dichloro-3-(2,4,6-trifluorophenyl)-pyrido[2,3-d]pyridazine as a yellow foamy glass (0.11 g).

¹H NMR (CDCl₃) δ ppm: 6.90 (m, 2H), 9.80 (s, 1H), 10.0 (s, H).

Step 4

Isopropylamine (1.5 ml) was added to the product from Step 3 (0.020 g) in DCM and the tube stoppered and the reaction stirred overnight at room temperature. The DCM was evaporated and water added to the residue, which was then extracted with DCM. The extract was dried over magnesium sulphate and evaporated to give an orange oil, which was purified by HPLC eluting with ethyl acetate:hexane 4:1 to give [2-Chloro-3-(2,4,6-trifluorophenyl)-pyrido[2,3-d]pyridazin-4-yl]-isopropylamine (0.007 g)

¹H NMR (CDCl₃) δ ppm: 1.27 (d, 6H), 4.05 (m, 1H), 4.90 (bs, 1H), 6.92 (m, 2H), 9.55 (s, 1H), 9.90 (s, 1H).

EXAMPLE 5

This Example illustrates the preparation of [7-chloro-6-(2,4,6-trifluorophenyl)-pyrido[2,3-c]pyridazin-5-yl]-isopropylamine (Compound No. 3, Table 26).

Step 1

3-Aminopyridazine-4-carboxylic acid (1.68 g, prepared as in JOC, (1985), 50, 346) was refluxed in ethanol (170 ml) with concentrated hydrochloric acid (2 ml) and p-toluene-sulphonyl chloride (0.1 g) for 55 hours. The solvent was evaporated and ice water added to the residue, which was then neutralised with solid sodium bicarbonate. The mixture was extracted with chloroform, insoluble material filtered, the organic extract dried over magnesium sulphate and evaporated to give 3-aminopyridazine-4-carboxylic acid ethyl ester (1.02 g) as a white solid.

¹H NMR (CDCl₃) δ ppm: 1.40 (t, 3H), 4.40 (q, 2H), 6.50 (bs, 2H), 7.74 (d, 1H), 8.72 (d, 1H).

Step 2

The product from Step 1 (0.36 g) was dissolved in dry toluene (25 ml) and DMAP (0.262 g) was added. A solution of 2,4,6-trifluorophenylacetyl chloride (0.45 g) in dry toluene (1 ml) was added dropwise with stirring, and a white precipitate formed. After stirring at room temperature for 10 minutes the reaction was stirred under reflux for 4.5 hours, and then allowed to stand overnight at room temperature. The white solid was filtered and washed with toluene, and the filtrate evaporated to give a brown oil, which was purified by HPLC eluting with ethyl acetate:hexane 4:1 to give 3-[2-(2,4,6-trifluorophenyl)-acetylamino]-pyridazine-4-carboxylic acid ethyl ester as a pale yellow solid (0.57 g), m.p. 135° C.

¹H NMR (CDCl₃) δ ppm: 1.40 (t, 3H), 4.22 (s, 2H), 4.41 (q, 2H), 6.70 (m, 2H), 7.94 (d, 1H), 9.15 (d, 1H), 10.30 (bs, 1H).

Step 3

The product from Step 2 (2.0 g) was dissolved in dry THF (50 ml), and sodium bistrimethylsilylamide (17.7 ml of a 1.0M solution in THF) was added dropwise with stirring under nitrogen at 0° C. The reaction was stirred for 3 hours at 0° C. and a yellow precipitate was formed. The reaction was quenched with concentrated hydrochloric acid and then poured into ice water. The solid was filtered, washed with water and air dried to give 6-(2,4,6-trifluorophenyl)-8H-pyrido[2,3-c]pyridazine-5,7-dione as a yellow solid (1.92 g), m.p. >330° C., still containing some THF, which was used without further purification.

¹H NMR (D₆-DMSO) δ ppm: 7.30 (m, 2H), 8.10 (d, 1H), 9.20 (d, 1H), 11.90 (bs, 1H), 12.60 (s, 1H).

Step 4

The product from Step 3 (0.060 g) was heated to 90° C. in phosphorus oxychloride (1 ml) for 1 hour to give a clear black solution. The mixture was cooled and the excess in phosphorus oxychloride evaporated. The residue was quenched with ice and aqueous sodium bicarbonate, extracted with ethyl acetate, the extract dried over magnesium sulphate and evaporated to give 5,7-dichloro-6-(2,4,6-trifluorophenyl)-pyrido[2,3-c]pyridazine as a black solid (0.087 g).

¹H NMR (CDCl₃) δ ppm: 6.90 (m, 2H), 8.30 (d, 1H), 9.75 (d, 1H).

Step 4

The product from Step 3 (0.080 g) was stirred with isopropylamine (2 ml) in DCM (5 ml) at room temperature overnight and then heated to 40° C. in a sealed tube for 4 hours. The volatiles were evaporated, water was added and the mixture extracted with DCM. The extracts were dried over magnesium sulphate and evaporated to give a dark brown tar, which was purified by preparative TLC on silica gel plates eluting with ethyl acetate:hexane 3:2 to give [7-Chloro-6-(2,4,6-trifluorophenyl)-pyrido[2,3-c]pyridazin-5-yl]-isopropylamine (0.008 g),

¹H NMR (CDCl₃) δ ppm: 1.20 (d, 6H), 3.71 (m, 1H), 4.45 (bs, 1H), 6.87-6.92 (m, 2H), 7.97 (d, 1H), 9.37 (d, 1H).

TABLE 133 NMR data (ppm, in CDCl₃, Compound Table Compound unless otherwise No. No. Structure stated) or Mpt.   3  1

1.1 (d, 6 H), 3.26 (m, 1 H), 6.84 (m, 2 H),6.95 (bd, 1 H), 8.67 (d, 1 H), 9.0 (d, 1 H).   4  1

0.8 (t, 3 H), 1.27 (m, 2 H), 1.55 (m, 2 H),2.87 (m, 2 H), 6.8, 6.85 (ABd, 2 H); 8.66,8.99 (ABd, 2 H).   14  1

129-131° C.   15  1

149-150° C.   16  1

175-177° C.   17  1

153-155° C.   22  1

0.92 (m) + 1.22 (m) + 1.55 (m)(total = 8 H), 2.9 (m, 2 H), 6.85 (m, 2 H),8.78, 8.96 (ABd, 2 H).   23  1

151-153° C.   58  1

102-104° C.  108  1

1.12 (d, 3 H), 3.27 (m, 2 H), 3.3 (s, 3 H),3.5 (m, 1 H), 6.8 (m, 2 H), 8.67 (d) + 8.97 (ABd)(total = 2 H)  161  1

138-140° C.  162  1

140-141° C.  219  1

3.0 (s, 6 H), 6.85 (m, 2 H), 8.65,8.87 (ABd, 2 H)   3  5

157-159° C.   4  5

0.82 (m, 3 H), 1.22 m + 1.5 m (total = 4 H),2.82 (m, 2 H), 7.1-7.47 (m, 3 H), 8.67 + 9.05(ABd, 2 H).   17  5

159-160° C.   20  5

166-168° C.   22  5

163-165° C.   23  5

163-165° C.   28  5

 71-73° C.  108  5

1.05 (d) + 1.12 (d) (total = 3 H), 3.1-3.5(m, 3 H), 3.25 (d) + 3.32 (d) (total = 3 H),7.1 (m) + 7.4 (m) (total = 4 H), 8.67(d, 1 H), 9.06 (d, 1 H)  161  5

0.82 (m, 4 H), 3.65 (m, 4 H), 7.12-7.35(m, 3 H), 8.66 + 8.87 (ABd, 2 H).  162  5

1.52 (m, 6 H), 3.3 (m, 4 H), 7.25 (m) + 7.4 (m)(total = 3 H), 8.78 + 8.95 (ABd, 2 H).  171  5

2.3 (s, 3 H), 2.5 (m, 4 H), 7.15 (m, 1 H),7.37 (m, 2 H), 8.75 (d, 1 H), 8.92 (d, 1 H).   3  11

1.16 (d, 6 H), 3.41 (m, 1 H), 6.85 (dd, 2 H),7.79 (bs, 1 H), 7.84 (d, 1 H). 9.40 (d, 1 H).   23  11

0.79 (t, 3 H), 1.11 (d, 3 H), 1.47 (m, 2 H),3.13 (m, 1 H), 6.86 (dd, 2 H), 7.79 (bs,1 H), 7.84 (d, 1 H), 9.40 (d, 1 H).   3  21

1.27 (d, 6 H), 4.05 (m, 1 H), 4.90 (bs, 1 H),6.92 (m, 2 H), 9.55 (s, 1 H), 9.90 (s, 1 H).   3  26

1.20 (d, 6 H), 3.71 (m, 1 H), 4.45 (bs, 1 H),6.87-6.92 (m, 2 H), 7.97 (d, 1 H), 9.37 (d, 1 H).   3  31

1.25 (d, 6 H), 4.5 (bd, 1 H), 4.6 (m, 1 H),7.15 (t, 2 H), 7.6 (m, 1 H), 8.625 (fd, 1 H),8.85 (fd, 1 H).   3  32

1.10 (d, 6 H), 4.52 (m, 2 H), 7.28 (m, 3 H),7.47 (m, 1 H), 8.52 (d, 1 H), 8.76 (d, 1 H)   23  32

0.78 (m, 3 H), 1.07 (m, 3 H), 1.45 (m, 2 H),4.48 (m, 2 H), 7.25 (m, 3 H), 7.50 (m, 1 H),8.51 (d, 1 H), 8.71 (d, 1 H)   3  37

160-161° C.   16  37

181-183° C.  171  37

2.3 (s, 3 H), 2.5 (m, 3 H), 3.2-3.5 (m, 4 H),7.27 (m) + 7.4 (m) + 7.62 (m) (total = 3 H), 8.77(d, 1 H), 8.92 (d, 1 H).   3  43

1.10 (d, 6 H), 4.32 (d, 1 H), 4.57 (m,1 H), 7.22 (m, 1 H), 7.35 (m, 1 H), 7.48(m, 1 H), 7.78 (m, H), 8.53 (d, 1 H), 8.71(d, 1 H)   23  43

0.81 (m, 3 H), 1.10 (m, 3 H), 1.40 (m,2 H), 4.26 (m, 1 H), 4.45 (m, 1 H), 7.25 (m,1 H), 7.38 (m, 1 H), 7.50 (m, 1 H), 7.76(m, 1 H), 8.52 (d, 1 H), 8.74 (d, 1 H)   3 103

127-128° C.   5 103

138-140° C.   12 103

106-108° C.   14 103

120-121° C.   15 103

153-154° C.   23 103

101-102° C.   58 103

 99-100° C.   92 103

1.07 (t, 3 H), 1.57 (s, 3 H), 3.52 (s, 2 H), 3.72(q, 2 H), 4.85 (m, 2 H), 6.85 (m, 2 H), 8.8 (d,1 H), 9.0 (d, 1 H).  161 103

148-150° C.  171 103

167-160° C.  2651 103

100-101° C.  2660 103

1.3 (d, 3 H), 1.4 (d, 3 H), 3.9 (m, 1 H), 6.95-7.6(m, 4 H), 8.75 (m, 1 H), 9.05 (m, 1 H).  2671 103

123-124° C.  2706 103

0.8 (m, 6 H), 1.72 (m, 1 H), 2.6 (m, 2 H), 7.02-7.47 (m, 4 H), 8.6 (d, 1 H), 8.92 (d, 1 H). 43704 103

133-135° C.(diastereoisomer 1) 43704 103

137-139° C.(diastereoisomer 2) 43715 103

118-119° C. 43750 103

0.80 (d) + 0.83 (d) (total = 6 H), 1.72 (m, 1 H),2.65 (m, 2 H), 7.1-7.3 (m) + 7.35, 7.6 (d)(total = 3 H), 8.6 (d, 1 H), 8.92 (d, 1 H).   1 128

4.03 (s, 5 H), 6.74 (t, 2 H), 8.43 (d, 1 H), 8.61(d, 1 H), 10.9 (s, 1 H).   6 128

162-163° C.   12 128

158-159° C.   13 128

1.48 (t, 3 H), 4.52 (q, 2 H), 6.73 (d, 1 H),8.75 (d, 1 H).   25 128

1.45 (t, 3 H), 3.90 (s, 2 H), (4.45 (q, 2 H), 6.75(m, 2 H), 9.45 (s1 H), 10.60 (s, 1 H), 11.1 (bs,1 H).   37 128

1.40 (t, 3 H), 4.22 (s, 2 H), 4.41 (q, 2 H),6.70 (m, 2 H), 7.94 (d, 1 H), 9.15 (d, 1 H), 10.30(bs, 1 H).   1 129

(d⁶-DMSO) 7.25(t, 2 H), 8.6(fd, 1 H), 8.7(fd,1 H), 12.6(s, 1 H).   6 129

>220° C.   9 129

250-252° C.   11 129

258° C.   12 129

>200° C.   13 129

(CD₃OD) 6.83 (2d, 2 H), 7.44 (d, 1 H),9.00 (d, 1 H).   25 129

(D⁶-DMSO) 7.25 (m, 2 H), 9.17 (s, 1 H),9.47 (s, 1 H), 12.30 (bs, 1 H).   37 129

(D₆-DMSO) 7.30 (m, 2 H), 8.10 (d, 1 H),9.20 (d, 1 H), 11.90 (bs, 1 H), 12.60 (s, 1 H).   1 130

139-141° C.   6 130

154-155° C.   9 130

7.21 (m, 1 H), 7.28(m, 2 H), 7.48(m, 1 H),8.95(d, 1 H), 9.08(d, 1 H).   11 130

7.18(d, 1 H), 7.29(m, 1 H), 7.41(t, 1 H),7.69(dd, 1 H), 9.00(d, 1 H), 9.09(d, 1 H).   12 130

159-160° C.   13 130

6.92 (m, 2 H), 8.11 (d, 1 H), 9.71 (d, 1 H).   25 130

6.90 (m, 2 H), 9.80 (s, 1 H), 10.0 (s, 1 H).   37 130

6.90 (m, 2 H), 8.30 (d, 1 H), 9.75 (d, 1 H).   1 131

120-121° C.   6 131

7.27 (m) + 7.55 (m) (total = 3 H), 9.07 (d, 1 H),9.2 (d, 1 H).   12 131

7.45 (m) + 7.67 (d) (total = 3 H), 9.07 (d, 1 H),9.2 (d, 1 H).

EXAMPLE 6

This Example illustrates the fungicidal properties of the compounds of the general formula (1).

Compounds were tested in a leaf disk assay, with methods described below. Test compounds were dissolved in DMSO, and diluted into water to 200 ppm.

Plasmopara viticola (downy mildew of grapevine): grapevine leaf disks were placed on agar in a 24-well plate and sprayed a solution of the test compound. After allowing to dry completely, for between 12 and 24 hours, the leaf disks were inoculated with a spore suspension of the fungus. After appropriate incubation the activity of a compound was assessed seven days after inoculation as preventive fungicidal activity. Phytophthora infestans (late blight of potato on tomato): tomato leaf disks were placed on water agar in a 24-well plate and sprayed with a solution of the test compound. After allowing to dry completely, for between 12 and 24 hours, the leaf disks were inoculated with a spore suspension of the fungus. After appropriate incubation the activity of a compound was assessed four days after inoculation as preventive fungicidal activity. Erysiphe graminis f.sp. hordei (barley powdery mildew): barley leaf segments were placed on agar in a 24-well plate and sprayed with a solution of the test compound. After allowing to dry completely, for between 12 and 24 hours, the leaf disks were inoculated with a spore suspension of the fungus. After appropriate incubation the activity of a compound was assessed four days after inoculation as preventive fungicidal activity. Erysiphe graminis f.sp. tritici (wheat powdery mildew): wheat leaf segments were placed on agar in a 24-well plate and sprayed with a solution of the test compound. After allowing to dry completely, for between 12 and 24 hours, the leaf disks were inoculated with a spore suspension of the fungus. After appropriate incubation the activity of a compound was assessed four days after inoculation as preventive fungicidal activity. Puccinia recondita f.sp. tritici (wheat brown rust): wheat leaf segments were placed on agar in a 24-well plate and sprayed with a solution of the test compound. After allowing to dry completely, for between 12 and 24 hours, the leaf disks were inoculated with a spore suspension of the fungus. After appropriate incubation the activity of a compound was assessed nine days after inoculation as preventive fungicidal activity. Septoria nodorum (wheat glume blotch): wheat leaf segments were placed on agar in a 24-well plate and sprayed with a solution of the test compound. After allowing to dry completely, for between 12 and 24 hours, the leaf disks were inoculated with a spore suspension of the fungus. After appropriate incubation the activity of a compound was assessed four days after inoculation as preventive fungicidal activity. Pyrenophora teres (barley net blotch): barley leaf segments were placed on agar in a 24-well plate and sprayed with a solution of the test compound. After allowing to dry completely, for between 12 and 24 hours, the leaf disks were inoculated with a spore suspension of the fungus. After appropriate incubation the activity of a compound was assessed four days after inoculation as preventive fungicidal activity. Pyricularia oryzae (rice blast): rice leaf segments were placed on agar in a 24-well plate and sprayed with a solution of the test compound. After allowing to dry completely, for between 12 and 24 hours, the leaf disks were inoculated with a spore suspension of the fungus. After appropriate incubation the activity of a compound was assessed four days after inoculation as preventive fungicidal activity. Botrytis cinerea (grey mould): bean leaf disks were placed on agar in a 24-well plate and sprayed with a solution of the test compound. After allowing to dry completely, for between 12 and 24 hours, the leaf disks were inoculated with a spore suspension of the fungus. After appropriate incubation the activity of a compound was assessed four days after inoculation as preventive fungicidal activity. The following compounds gave greater than 60% control of disease: Plasmopara viticola, Compounds 4 (1), 20 (1), 23 (5); Phytophthora infestans, Compounds 3 (1), 58 (5), 3 (103); Erysiphe graminis f.sp. hordei, Compounds 3 (1), 14 (1), 15 (1), 16 (1), 17 (1), 22 (1), 23 (1), 58 (1), 108 (1), 161 (1), 162 (1), 3 (5), 4 (5), 17 (5), 20 (5), 22 (5), 23 (5), 28 (5), 58 (5), 108 (5), 162 (5), 171 (5), 665 (31), 23 (32), 3 (37), 16 (37), 171 (37), 665 (37), 678 (37), 3 (43), 23 (43), 685 (43), 3 (103), 12 (103), 23 (103), 58 (103), 92 (103), 2651 (103), 2660 (103), 2671 (103), 23844 (103) diastereoisomer 1, 23844 (103) diastereoisomer 2, 23855 (103), 23890 (103;

Erysiphe graminis f.sp. tritici, Compounds 3 (1), 4 (1), 15 (1), 16 (1), 2291), 23 (1), 58 (1), 108 (1), 162 (1), 219 (1), δ 95), 161 (5), 3 (31), 16 (37), 665 (37), 3 (103), 12 (103), 23 (103), 58 (103), 92 (103), 2651 (103), 2660 (103), 2671 (103), 23844 (103) diastereoisomer 1, 23844 (103) diastereoisomer 2, 23855 (103), 23890 (103);

Puccinia recondita f.sp. tritici, Compounds 3 (1), 14 (1), 15 (1), 16 (1), 17 (1), 23 (1), 58 (1), 108 (1), 161 (1), 162 (1), 4 (5), 17 (5), 23 (5), 28 (5), 58 (5), 108 (5), 3 (31), 16 (37), 665 (37), 678 (37), 3 (103), 12 (103), 23 (103), 58 (103), 92 (103), 2651 (103), 2660 (103), 2671 (103), 23844 (103) diastereoisomer 1, 23855 (103), 23890 (103); Septoria nodorum, Compounds 391), 15 (1), 16 (1), 17 (1), 23 (1), 58 (1), 5895), 161 (5), 22 (6), 665 (37), 685 (43), 12 (103), 23 (103), 58 (103), 2660 (103), 2671 (103), 23844 (103) diastereoisomer 1, 23855 (103), 23890 (103); Pyrenophora teres, Compounds 3 (1), 14 (1), 15 (1), 16 (1), 17 (1), 23 (1), 58 (1), 161 (1), 3 (5), 20 (5), 16 (37), 665 (37), 3 (103), 12 (103), 23 (103), 58 (103), 2651 (103), 2660 (103), 2671 (103), 23844 (103) diastereoisomer 1, 23855 (103), 23890 (103); Pyricularia oryzae, Compounds 3 (1), 4 (1), 14 (1), 15 (1), 16 (1), 17 (1), 20 (1), 23 (1), 58 (1), 108 (1), 161 (1), 3 (5), 4 (5), 20 (5), 23 (5), 58 (5), 108 (5), 3 (32), 3 (37), 16 (37), 678 (37), 3 (43), 3 (103), 12 (103), 23 (103), 58 (103), 92 (103), 171 (103), 2651 (103), 2669 (103), 2671 (103), 23844 (103) diastereoisomer 1, 23844 (103) diastereoisomer 2, 23855 (103), 23890 (103); Botrytis cinerea, Compounds 4 (1), 14 (1), 15 (1), 16 (1), 17 (1), 22 (1), 58 (1), 108 (1), 4 (5), 22 (5), 28 (5), 58 (5), 108 (5), 162 (5), 16 (37), 678 (37), 23 (103), 92 (103), 2651 (103), 2660 (103), 23844 (103) diastereoisomer 2, 23855 (103), 23890 (103). 

1. The compound of the general formula (1):

wherein W and X, X and Y or Y and Z are N and the other two are CR⁸; R⁸ is H, halo, C₁₋₄ alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkyl; R is halo; R¹ is halo, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl, C₁₋₈ alkoxy, C₁₋₈ alkylthio, aryl, aryloxy, arylthio, heteroaryl, heteroaryloxy, heteroarylthio, aryl(C₁₋₄)alkyl, aryl(C₁₋₄)alkoxy, heteroaryl(C₁₋₄)alkyl, heteroaryl(C₁₋₄)alkoxy, aryl(C₁₋₄)alkylthio, heteroaryl(C₁₋₄)alkylthio, morpholino, piperidino or pyrrolidino; R² is NR³R⁴; R³ and R⁴ are independently H, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, aryl, aryl(C₁₋₈)alkyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl, heteroaryl, heteroaryl(C₁₋₈)alkyl, NR⁵R⁶, provided that not both R³ and R⁴ are H or NR⁵R⁶, or R³ and R⁴ together form a C₃₋₇ alkylene or C₃₋₇ alkenylene chain optionally substituted with one or more C₁₋₄ alkyl or C₁₋₄ alkoxy groups, or, together with the nitrogen atom to which they are attached, R³ and R⁴ form a morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or piperazine N—(C₁₋₄)alkyl ring; and R⁵ and R⁶ are independently H, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, aryl, aryl(C₁₋₈)alkyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl (C₁₋₆)alkyl, heteroaryl or heteroaryl(C₁₋₈)alkyl; any of the foregoing alkyl, alkenyl, alkynyl or cycloalkyl groups or moieties (other than for R⁸) being optionally substituted with halogen, cyano, C₁₋₆ alkoxy, C₁₋₆ alkylcarbonyl, C₁₋₆ alkoxycarbonyl, C₁₋₆ haloalkoxy, C₁₋₆ alkylthio, tri(C₁₋₄)alkylsilyl, C₁₋₆ alkylamino or C₁₋₆ dialkylamino, any of the foregoing morpholine, thiomorpholine, piperidine, piperazine and pyrrolidine rings being optionally substituted with C₁₋₄ alkyl, and any of the foregoing aryl or heteroaryl groups or moieties being optionally substituted with one or more substituents selected from halo, hydroxy, mercapto, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ alkoxy, C₂₋₆ alkenyloxy, C₂₋₆ alkynyloxy, halo(C₁₋₆)alkyl, halo(C₁₋₆)alkoxy, C₁₋₆ alkylthio, halo(C₁₋₆)alkylthio, hydroxy(C₁₋₆)alkyl, C₁₋₄ alkoxy(C₁₋₆)alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenoxy, benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato, isothiocyanato, nitro, —NR′″R″″, —NHCOR′″, —NHCONR′″R″″, —CONR′″R″″, —SO₂R′″, —OSO₂R′″, —COR′″, —CR′″═NR″″ or —N═CR′″R″″, in which R′″ and R″″ are independently hydrogen, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy, halo(C₁₋₄)alkoxy, C₁₋₄ alkylthio, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenyl or benzyl, the phenyl and benzyl groups being optionally substituted with halogen, C₁₋₄ alkyl or C₁₋₄ alkoxy.
 2. A compound according to claim 1 wherein R³ is C₁₋₈ alkyl, halo(C₁₋₈)alkyl, hydroxy(C₁₋₈)alkyl, C₁₋₄ alkoxy(C₁₋₈)alkyl, C₁₋₄ alkoxyhalo-(C₁₋₈)alkyl, tri(C₁₋₄)alkylsilyl(C₁₋₆)alkyl, C₁₋₄ alkylcarbonyl(C₁₋₈)alkyl, C₁₋₄ alkylcarbonyl-halo(C₁₋₈)alkyl, phenyl(1-4)alkyl, C₂₋₈ alkenyl, halo(C₂₋₈)alkenyl, C₂₋₈ alkynyl, C₃₋₈ cycloalkyl optionally substituted with chloro, fluoro or methyl, C₃₋₈ cycloalkyl(C₁₋₄)alkyl, phenylamino, piperidino or morpholino, the phenyl ring of phenylalkyl or phenylamino being optionally substituted with one, two or three substituents selected from halo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy and halo(C₁₋₄)alkoxy; and R⁴ is H, C₁₋₄ alkyl, halo(C₁₋₄)alkyl or amino, or R³ and R⁴ together form a C₃₋₇ alkylene or alkenylene chain optionally substituted with methyl, or, together with the nitrogen atom to which they are attached, R³ and R⁴ form a morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or piperazine N—(C₁₋₄)alkyl ring, in which the morpholine or piperazine rings are optionally substituted with methyl.
 3. A compound according to claim 1 wherein R¹ is phenyl optionally substituted with from one to five halogen atoms or with from one to three substituents selected from halo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkoxy, pyridyl optionally substituted with from one to four halogen atoms or with from one to three substituents selected from halo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkoxy, 2- or 3-thienyl optionally substituted with from one to three halogen atoms or with from one to three substituents selected from halo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkoxy, or piperidino or morpholino both optionally substituted with one or two methyl groups.
 4. A compound according to claim 4 wherein R¹ is 2,6-difluorophenyl, 2-fluoro-6-chlorophenyl, 2,5,6-trifluorophenyl, 2,4,6-trifluorophenyl, 2,6-difluoro-4-methoxyphenyl or pentafluorophenyl.
 5. A compound according to claim 1 wherein R⁸ is H, halo, C₁₋₄ alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkyl; R is halo; R¹ is halo, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl, C₁₋₈ alkoxy, C₁₋₈ alkylthio, aryl, aryloxy, arylthio, heteroaryl, heteroaryloxy, heteroarylthio, aryl(C₁₋₄)alkyl, aryl(C₁₋₄)alkoxy, heteroaryl(C₁₋₄)alkyl, heteroaryl(C₁₋₄)alkoxy, aryl(C₁₋₄)-alkylthio, heteroaryl(C₁₋₄)alkylthio, morpholino, piperidino or pyrrolidino; R² is NR³R⁴; R³ and R⁴ are independently H, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, aryl, aryl(C₁₋₈)alkyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl, heteroaryl, heteroaryl(C₁₋₈)alkyl, NR⁵R⁶, provided that not both R³ and R⁴ are H or NR⁵R⁶, or R³ and R⁴ together form a C₃₋₇ alkylene or C₃₋₇ alkenylene chain optionally substituted with one or more C₁₋₄ alkyl or C₁₋₄ alkoxy groups, or, together with the nitrogen atom to which they are attached, R³ and R⁴ form a morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or piperazine N—(C₁₋₁₄)alkyl ring; and R⁵ and R⁶ are independently H, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, aryl, aryl(C₁₋₈)alkyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl, heteroaryl or heteroaryl(C₁₋₈)alkyl; any of the foregoing alkyl, alkenyl, alkynyl or cycloalkyl groups or moieties (other than for R⁸) being optionally substituted with halogen, cyano, C₁₋₆ alkoxy, C₁₋₆ alkylcarbonyl, C₁₋₆ alkoxycarbonyl, C₁₋₆ haloalkoxy, C₁₋₆ alkylthio, tri(C₁₋₄)alkylsilyl, C₁₋₆ alkylamino or C₁₋₆ dialkylamino, any of the foregoing morpholine, thiomorpholine, piperidine, piperazine and pyrrolidine rings being optionally substituted with C₁₋₄ alkyl, and any of the aryl, heteroaryl, aryloxy or heteroaryl groups being optionally substituted with one or more substituents selected from halo, hydroxy, mercapto, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ alkoxy, C₂₋₆ alkenyloxy, C₂₋₆ alkynyloxy, halo(C₁₋₆)alkyl, halo(C₁₋₆)alkoxy, C₁₋₆ alkylthio, halo(C₁₋₆)alkylthio, hydroxy(C₁₋₆)alkyl, C₁₋₄ alkoxy(C₁₋₆)alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenoxy, benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato, isothiocyanato, nitro, —NR′″R″″, —NHCOR′″, —NHCONR′″R″″, —CONR′″R″″, —SO₂R′″, —OSO₂R′″, —COR′″, —CR′″═NR″″ or —N═CR′″R″″, in which R′″ and R″″ are independently hydrogen, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy, halo(C₁₋₄)alkoxy, C₁₋₄ alkylthio, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenyl or benzyl, the phenyl and benzyl groups being optionally substituted with halogen, C₁₋₄ alkyl or C₁₋₄ alkoxy.
 6. A compound according to claim 1 wherein R⁸ is H, halo, C₁₋₄ alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkyl; R is halo; R¹ is halo, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl, C₁₋₈ alkoxy, C₁₋₈ alkylthio, aryl, aryloxy, arylthio, heteroaryl, heteroaryloxy, heteroarylthio, aryl(C₁₋₄)alkyl, aryl(C₁₋₄)alkoxy, heteroaryl(C₁₋₄)alkyl, heteroaryl(C₁₋₄)alkoxy, aryl(C₁₋₄)alkylthio, heteroaryl(C₁₋₄)alkylthio, morpholino, piperidino or pyrrolidino; R² is NR³⁴; R³ is C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₂₋₄ alkenyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl or phenylamino in which the phenyl ring is optionally substituted with one, two or three substituents selected from halo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy and halo(C₁₋₄)alkoxy; and R⁴ is H, C₁₋₄ alkyl or amino, or R³ and R⁴ together form a C₄₋₆ alkylene chain optionally substituted with C₁₋₄ alkyl or C₁₋₄ alkoxy, or, together with the nitrogen atom to which they are attached, R³ and R⁴ form a morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or piperazine N—(C₁₋₄)alkyl ring; any of the alkyl, alkenyl, alkynyl or cycloalkyl groups or moieties (other than for R⁸) being optionally substituted with halogen, cyano, C₁₋₆ alkoxy, C₁₋₆ alkylcarbonyl, C₁₋₆ alkoxycarbonyl, C₁₋₆ haloalkoxy, C₁₋₆ alkylthio, tri(C₁₋₄)alkylsilyl, C₁₋₆ alkylamino or C₁₋₆ dialkylamino, any of the foregoing morpholine, thiomorpholine, piperidine, piperazine and pyrrolidine rings being optionally substituted with C₁₋₄ alkyl, and any of the aryl or heteroaryl groups or moieties being optionally substituted with one or more substituents selected from halo, hydroxy, mercapto, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ alkoxy, C₂₋₆ alkenyloxy, C₂₋₆ alkynyloxy, halo(C₁₋₆)alkyl, halo(C₁₋₆)alkoxy, C₁₋₆ alkylthio, halo(C₁₋₆)alkylthio, hydroxy(C₁₋₆)alkyl, C₁₋₄ alkoxy(C₁₋₆)alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenoxy, benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato, isothiocyanato, nitro, —NR′″R″″, —NHCOR′″, —NHCONR′″R″″, —CONR′″R″″, —SO₂R′″, —OSO₂R′″, —COR′″, —CR′″═NR″″ or —N═CR′″R″″, in which R′″ and R″″ are independently hydrogen, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy, halo(C₁₋₄)alkoxy, C₁₋₄ alkylthio, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenyl or benzyl, the phenyl and benzyl groups being optionally substituted with halogen, C₁₋₄ alkyl or C₁₋₄ alkoxy.
 7. A compound according to claim 1 wherein R⁸ is H, halo, C₁₋₄ alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkyl; R is halo; R¹ is optionally substituted phenyl; R² is NR³R⁴; R³ and R⁴ are independently H, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, aryl, aryl(C₁₋₈)alkyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl, heteroaryl, heteroaryl(C₁₋₈)alkyl, NR⁵R⁶, provided that not both R³ and R⁴ are H or NR⁵R⁶, or R³ and R⁴ together form a C₃₋₇ alkylene or C₃₋₇ alkenylene chain optionally substituted with one or more C₁₋₄ alkyl or C₁₋₄ alkoxy groups, or, together with the nitrogen atom to which they are attached, R³ and R⁴ form a morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or piperazine N—(C₁₋₄)alkyl ring; and R⁵ and R⁶ are independently H, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, aryl, aryl(C₁₋₈)alkyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl, heteroaryl or heteroaryl(C₁₋₈)alkyl; any of the alkyl, alkenyl, alkynyl or cycloalkyl groups or moieties (other than for R⁸) being optionally substituted with halogen, cyano, C₁₋₆ alkoxy, C₁₋₆ alkylcarbonyl, C₁₋₆ alkoxycarbonyl, C₁₋₆ haloalkoxy, C₁₋₆ alkylthio, tri(C₁₋₄)alkylsilyl, C₁₋₆ alkylamino or C₁₋₆ dialkylamino, any of the foregoing morpholine, thiomorpholine, piperidine, piperazine and pyrrolidine rings being optionally substituted with C₁₋₄ alkyl, and any of the aryl or heteroaryl groups or moieties, including the phenyl group of R¹, being optionally substituted with one or more substituents selected from halo, hydroxy, mercapto, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ alkoxy, C₂₋₆ alkenyloxy, C₂₋₆ alkynyloxy, halo(C₁₋₆)alkyl, halo(C₁₋₆)alkoxy, C₁₋₆ alkylthio, halo(C₁₋₆)alkylthio, hydroxy(C₁₋₆)alkyl, C₁₋₄ alkoxy(C₁₋₆)alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₁₄)alkyl, phenoxy, benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato, isothiocyanato, nitro, —NR′″R″″, —NHCOR′″, —NHCONR′″R″″, —CONR′″R″″, —SO₂R′″, —OSO₂R′″, —COR′″, —CR′″═NR″″ or —N═CR′″R″″, in which R′″ and R″″ are independently hydrogen, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy, halo(C₁₋₄)alkoxy, C₁₋₄ alkylthio, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenyl or benzyl, the phenyl and benzyl groups being optionally substituted with halogen, C₁₋₄ alkyl or C₁₋₄ alkoxy.
 8. A compound according to claim 1 wherein R⁸ is H, halo, C₁₋₄ alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkyl; R is halo; R¹ is phenyl optionally substituted with from one to five halogen atoms or with from one to three substituents selected from halo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkoxy, pyridyl optionally substituted with from one to four halogen atoms or with from one to three substituents selected from halo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkoxy, 2- or 3-thienyl optionally substituted with from one to three halogen atoms or with from one to three substituents selected from halo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkoxy, or piperidino or morpholino both optionally substituted with one or two methyl groups; R² is NR³R⁴; R³ is C₁₋₈ alkyl, halo(C₁₋₈)alkyl, hydroxy(C₁₋₈)alkyl, C₁₋₄ alkoxy(C₁₋₈)alkyl, C₁₋₄ alkoxyhalo-(C₁₋₈)alkyl, tri(C₁₋₄)alkylsilyl(C₁₋₆)alkyl, C₁₋₄ alkylcarbonyl(C₁₋₈)alkyl, C₁₋₄ alkylcarbonyl-halo(C₁₋₈)alkyl, phenyl(₁₋₄)alkyl, C₂₋₈ alkenyl, halo(C₂₋₈)alkenyl, C₂₋₈ alkynyl, C₃₋₈ cycloalkyl optionally substituted with chloro, fluoro or methyl, C₃₋₈ cycloalkyl(C₁₋₄)alkyl, phenylamino, piperidino or morpholino, the phenyl ring of phenylalkyl or phenylamino being optionally substituted with one, two or three substituents selected from halo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy and halo(C₁₋₄)alkoxy; and R⁴ is H, C₁₋₄ alkyl, halo(C₁₋₄)alkyl or amino, or R³ and K⁴ together form a C₃₋₇ alkylene or C₃₋₇ alkenylene chain optionally substituted with methyl, or, together with the nitrogen atom to which they are attached, R³ and R⁴ form a morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or piperazine N—(C₁₋₄)alkyl ring, in which the morpholine or piperazine rings are optionally substituted with methyl.
 9. A compound according to claim 1 wherein R⁸ is H, halo, C₁₋₄ alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkyl; R is halo; R¹ is phenyl optionally substituted with from one to five halogen atoms or with from one to three substituents selected from halo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkoxy; R² is NR³R⁴; R³ is C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₂₋₄ alkenyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl or phenylamino in which the phenyl ring is optionally substituted with one, two or three substituents selected from halo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy and halo(C₁₋₄)alkoxy; and R⁴ is H, C₁₋₄ alkyl or amino, or R³ and R⁴ together form a C₄₋₆ alkylene chain optionally substituted with methyl, or, together with the nitrogen atom to which they are attached, R³ and R⁴ form a morpholine ring.
 10. A process for preparing a compound of the general formula (1) according to claim 1 wherein R is chloro or fluoro and R² is NR³R⁴ and W, X, Y, Z, R¹, R³ and R⁴ are as defined in claim 1, which comprises reacting an amine of the general formula NR³R⁴ with a compound of the general formula (6) or (13)


11. The intermediate chemicals having the general formulae (4), (5), (6) and (13):

wherein W, X, Y, Z and R¹ are as defined in claim 1 and R⁷ is C₁₋₄ alkyl, other than the compound of formula (6) wherein X and Y are N, W and Z are C—Cl and R¹ is Cl.
 12. A plant fungicidal composition comprising a fungicidally effective amount of a compound as defined in claim 1 and a suitable carrier or diluent therefor.
 13. A method of combating or controlling phytopathogenic fungi which comprises applying to a plant, to a seed of a plant, to the locus of the plant or seed or to soil or to any other plant growth medium, a fungicidally effective amount of a compound according to claim 1 or a composition according to claim
 13. 